Impact of residual retinal fluid on treatment outcomes in neovascular age-related macular degeneration.

Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed.

Dexamethasone intravitreal implant in treatment-naïve diabetic macular oedema: findings from the prospective, multicentre, AUSSIEDEX study.

AIM: To evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME). METHODS: The open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks. RESULTS: Of 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and -89.6 µm (p<0.001), respectively, with a mean 2.5 injections. The change in mean CRT from baseline was -55.8 µm at week 16 (p<0.001). The most common adverse event was increased intraocular pressure (IOP), with 20.0% of eyes requiring IOP-lowering medication. One patient was discontinued due to increased IOP. No eyes required filtration surgery. No serious, treatment-related ocular adverse events were reported. CONCLUSION: In this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME. TRIAL REGISTRATION NUMBER: NCT02731911.

Longer treatment intervals are associated with reduced treatment persistence in neovascular age related macular degeneration.

AIMS: To test the hypothesis that patients treated for neovascular age related macular degeneration (nAMD) with longer treatment intervals are more likely to persist with treatment. METHODS: Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Treatment interval at 2 years was stratified based on the mean treatment interval over the three visits prior to and including the 2-year visit. Rates of non-persistence to follow-up were assessed from 2 to 5 years. RESULTS: Data from 1538 eyes were included. The overall rate of non-persistence was 51% at 5 years. Patients on longer treatment intervals (12-weeks) at 2 years were found to be less persistent to long-term follow-up. These eyes were found to have fewer active disease visits in the first 2 years (40%) than eyes treated at 4-weekly intervals (66%, p < 0.001). In the multivariable analysis, better vision at 2 years was associated with a lower risk of non-persistence (hazards ratio [HR] [95% CI]: 0.95 [0.93, 0.97], P < 0.001), while longer treatment intervals (HR [95% CI]: 1.31 [0.95, 1.8] and 1.54 [1.15, 2.06] for 12-week and > 12-week intervals vs. 4-week intervals, respectively, P = 0.002) and older patients (HR [95% CI]: 1.03 [1.02, 1.04], p < 0.001) were at higher risk of non-persistence. CONCLUSIONS: We found that patients on longer treatment intervals at 2 years were more likely to be non-persistent with treatment in later years. Reinforcing the need for ongoing treatment is important for patients on longer intervals who may feel complacent or that treatment is no longer effective, particularly if newer, longer lasting agents become widely available.

Hemiretinal vein occlusion 12-month outcomes are unique with vascular endothelial growth factor inhibitors: data from the Fight Retinal Blindness! Registry.

BACKGROUND/AIMS: To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. METHODS: A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. RESULTS: At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits. CONCLUSIONS: HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes.

Efficacy and safety of brolucizumab versus aflibercept in eyes with early persistent retinal fluid: 96-week outcomes from the HAWK and HARRIER studies.

OBJECTIVE: Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER. METHODS: After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12. RESULTS: A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: -202 µm vs. -145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm. CONCLUSION: In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

Incidence, risk factors and outcomes of submacular haemorrhage with loss of vision in neovascular age-related macular degeneration in daily clinical practice: data from the FRB! registry.

PURPOSE: The main purpose of the study was to report the estimated incidence, cumulative rate, risk factors and outcomes of submacular haemorrhage (SMH) with loss of vision in neovascular age-related macular degeneration (nAMD) receiving intravitreal injections (IVT) of vascular endothelial growth factor (VEGF) inhibitor in routine clinical practice. METHODS: Retrospective analysis of treatment-naïve eyes receiving IVTs of VEGF inhibitors (ranibizumab, aflibercept or bevacizumab) for nAMD from 1 January 2010 to 31 December 2020 that were tracked the Fight Retinal Blindness! registry. Estimated incidence, cumulative rate and hazard ratios (HR) of SMH with loss of vision during treatment were measured using the Poisson regression, Kaplan-Meier survival curves and Cox proportional hazard models. RESULTS: We identified 7642 eyes (6425 patients) with a total of 135 095 IVT over a 10-year period. One hundred five eyes developed SMH with loss of vision with a rate of 1 per 1283 injections (0.08% 95% confidence interval [95% CI] [0.06; 0.09]). The estimated incidence [95% CI] was 4.6 [3.8; 5.7] SMH with loss of vision per year per 1000 treated patients during the study. The cumulative [95% CI] rate of SMH per patient did not increase significantly with each successive injection (p = 0.947). SMH cases had a mean VA drop of around 6 lines at diagnosis, which then improved moderately to a 4-line loss at 1 year. CONCLUSIONS: Submacular haemorrhage (SMH) with loss of vision is an uncommon complication that can occur at any time in eyes treated for nAMD in routine clinical practice, with only limited recovery of vision 1 year later.

THREE-YEAR TREATMENT OUTCOMES OF AFLIBERCEPT VERSUS RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: Data from the Fight Retinal Blindness! Registry.

PURPOSE: Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. METHODS: This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. RESULTS: We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. CONCLUSION: Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

THE IMPACT OF DISEASE ACTIVITY ON 5-YEAR OUTCOMES IN PATIENTS UNDERGOING TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the impact of disease activity on clinical outcomes in a "real-world" cohort with neovascular age-related macular degeneration over 5 years. METHODS: Data were obtained from the prospectively defined Fight Retinal Blindness! registry. Eyes were divided into tertiles based on the proportion of visits where choroidal neovascular lesion was active (low, moderate, and high) up until 5 years. RESULTS: Data from 2,109 eyes were included. The adjusted mean (95% confidence interval) visual acuity change was -0.5 letters (-1.8 to 1.1), 1.8 letters (0.2 to 3.4), and -2.5 letters (-4.2 to -1.3) in the low, moderate, and high activity groups respectively, P < 0.001. Eyes in the low activity group were more likely to develop macular atrophy (56, 47 and 26% in the low, moderate, and high activity groups respectively, P < 0.001) but less likely to develop subretinal fibrosis (27, 35 and 42% in the low, moderate, and high activity groups respectively, P < 0.001). CONCLUSION: Eyes with higher and lower levels of disease activity had poorer outcomes than eyes with moderate activity over 5 years, apparently because of the development of subretinal fibrosis or macular atrophy.

Three-Year Outcomes of Neovascular Age-Related Macular Degeneration in Eyes That Do Not Develop Macular Atrophy or Subretinal Fibrosis.

Purpose: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA). Methods: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked. Results: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01). Conclusions: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA. Translational Relevance: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD.

Dose Response in the Subthreshold Nanosecond Laser Trial in Early Stages of AMD: A LEAD Study Report.

BACKGROUND AND OBJECTIVE: To examine the association between treatment parameters and the progression to late age-related macular degeneration (AMD) in the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a randomized, controlled trial of a subthreshold nanosecond laser (SNL) for slowing disease progression in the early stages of AMD. PATIENTS AND METHODS: The association between treatment parameters early in the trial period for participants in the SNL arm of the LEAD study and time to develop late AMD during the 3-year trial duration was examined. Parameters included treatment energy at the baseline and 6-month visits and the number of laser spots visible on fundus autofluorescence (FAF) imaging taken at 6 and 12 months (taken as a proxy measure of early, adequate delivery of the laser treatment at the baseline and 6-month visits, respectively). RESULTS: A multivariable analysis revealed there were no significant associations between time to develop late AMD and number of FAF-visible laser spots at 6-months (adjusted P = .537) nor laser energy used at baseline (adjusted P = .910). No significant associations were also observed when evaluating FAF-visible spots at 12-months (adjusted P = .107) and the average laser energy used at baseline and 6 months (adjusted P = .558). CONCLUSIONS: This study did not find any evidence to suggest that there was a dose response for the effect of laser treatment using these treatment parameters on the progression of AMD. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:380-386.].

Extended intervals for wet AMD patients with high retreatment needs: informing the risk during COVID-19, data from real-world evidence.

BACKGROUND/OBJECTIVE: Some clinicians may be forced to temporarily extend treatment intervals in neovascular age-related macular degeneration (nAMD) eyes with frequent retreatments to reduce the number of visits during the COVID-19 pandemic. To provide an indication of what these outcomes may be, we studied eyes with active lesions with unplanned treatment interval extensions before the pandemic occurred. METHODS: We compared eyes with active disease despite ≤6 weekly injections whose next injection was extended to ≥7 weeks and those whose intervals were not extended. We identified 1559 (16%) of 9602 eyes from the Fight Retinal Blindness! (FRB!) registry (2013 and 2018) that fit this criteria. Eyes were further stratified into four groups by the mean interval over the following 6 months: (1) ≤6 weeks (81%), (2) 7-9 weeks (9%), (3) 10-12 weeks (5%) and (4) >12 weeks (5%). RESULTS: There was a significant loss in VA in eyes extended to >12 weeks compared to the non-extended group (adjusted VA change, mean (95% CI): ≤6 weeks, 0.4 (-1.5 to 2.2), versus >12 weeks, -4.7 (-7.4 to -2.1), letters, p = 0.03 and a threefold increase in relative risk of losing ≥15 letters (absolute risk (14% versus 4%, p < 0.01)). CONCLUSION: Mean VA remained stable for 6 months in eyes requiring frequent treatment despite retreatment interval extension up to 10-12 weeks. There was a significant short-term risk to vision when retreatment interval was extended beyond 12 weeks, hence extensions to this level should be considered cautiously. These data may be useful for physicians who are considering reducing visits to mitigate the risk of COVID-19.

ANALYSIS OF FLUID VOLUME AND ITS IMPACT ON VISUAL ACUITY IN THE FLUID STUDY AS QUANTIFIED WITH DEEP LEARNING.

PURPOSE: To investigate quantitative differences in fluid volumes between subretinal fluid (SRF)-tolerant and SRF-intolerant treat-and-extend regimens for neovascular age-related macular degeneration and analyze the association with best-corrected visual acuity. METHODS: Macular fluid (SRF and intraretinal fluid) was quantified on optical coherence tomography volumetric scans using a trained and validated deep learning algorithm. Fluid volumes and complete resolution was automatically assessed throughout the study. The impact of fluid location and volumes on best-corrected visual acuity was computed using mixed-effects regression models. RESULTS: Baseline fluid quantifications for 348 eyes from 348 patients were balanced (all P > 0.05). No quantitative differences in SRF/intraretinal fluid between the treatment arms was found at any study-specific time point (all P > 0.05). Compared with qualitative assessment, the proportion of eyes without SRF/intraretinal fluid did not differ between the groups at any time point (all P > 0.05). Intraretinal fluid in the central 1 mm and SRF in the 1-mm to 6-mm macular area were negatively associated with best-corrected visual acuity (-2.8 letters/100 nL intraretinal fluid, P = 0.007 and -0.20 letters/100 nL SRF, P = 0.005, respectively). CONCLUSION: Automated fluid quantification using artificial intelligence allows objective and precise assessment of macular fluid volume and location. Precise determination of fluid parameters will help improve therapeutic efficacy of treatment in neovascular age-related macular degeneration.

USING MICROPERIMETRY AND LOW-LUMINANCE VISUAL ACUITY TO DETECT THE ONSET OF LATE AGE-RELATED MACULAR DEGENERATION: A LEAD Study Report.

PURPOSE: To evaluate the performance of microperimetry and low-luminance visual acuity for detecting late age-related macular degeneration (AMD) onset. METHODS: Two hundred ninety-two individuals with bilateral large drusen in the Laser Intervention in the Early Stages of AMD study underwent best-corrected visual acuity, low-luminance visual acuity, and microperimetry testing as well as multimodal imaging to detect late (neovascular or atrophic) AMD onset. The performance of the change in the measurement from baseline of each of visual function test for detecting late AMD onset was compared. RESULTS: The area under the receiver operating characteristic curve for detecting neovascular and atrophic AMD onset was not significantly different for low-luminance visual acuity (area under the receiver operating characteristic curve = 0.71 and 0.56, respectively) and microperimetry (area under the receiver operating characteristic curve = 0.82 and 0.62, respectively) compared with best-corrected visual acuity (area under the receiver operating characteristic curve = 0.57 and 0.56, respectively; P ≥ 0.126 for all). There was also only a fair degree of agreement between the three visual function measures for detecting the onset of neovascular and atrophic AMD (κ ≥ 0.24). CONCLUSION: Microperimetry, low-luminance visual acuity, and best-corrected visual acuity demonstrate limited performance for detecting the earliest onset of late AMD. It remains to be established whether they perform better than current methods designed to enable self-detection of neovascular AMD onset, such as Amsler grid testing.

Examining the added value of microperimetry and low luminance deficit for predicting progression in age-related macular degeneration.

PURPOSE: To examine the added predictive value of microperimetric sensitivity and low luminance deficit (LLD; difference between photopic and low luminance visual acuity (VA)) to information from colour fundus photography (CFP) for progression to late age-related macular degeneration (AMD) in individuals with bilateral large drusen. METHODS: 140 participants with bilateral large drusen underwent baseline microperimetry testing, VA measurements and CFP. They were then reviewed at 6-monthly intervals to 36 months, to determine late AMD progression. Microperimetry pointwise sensitivity SD (PSD), LLD and the presence of pigmentary abnormalities on CFPs were determined. Predictive models based on these parameters were developed and examined. RESULTS: Baseline microperimetry PSD and presence of pigmentary abnormalities were both significantly associated with time to develop late AMD (p≤0.004), but LLD was not (p=0.471). The area under the receiver operating characteristic curve (AUC) for discriminating between eyes that progressed to late AMD based on models using microperimetry PSD (AUC=0.68) and LLD (AUC=0.58) alone was significantly lower than that based on CFP grading for the presence of pigmentary abnormalities (AUC=0.80; both p<0.005). Addition of microperimetry and/or LLD information to a model that included CFP grading did not result in any improvement in its predictive performance (AUC=0.80 for all; all p≥0.66). CONCLUSIONS: While microperimetry, but not LLD, was significantly and independently associated with AMD progression at the population level, this study observed that both measures were suboptimal at predicting progression at the individual level when compared to conventional CFP grading and their addition to the latter did not improve predictive performance.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Intraocular Pressure Changes and Vascular Endothelial Growth Factor Inhibitor Use in Various Retinal Diseases: Long-Term Outcomes in Routine Clinical Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! PARTICIPANTS: Treatment-naïve eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up. METHODS: Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice. MAIN OUTCOME MEASURES: The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up. RESULTS: We identified 3429 treatment-naïve eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was -0.5 mmHg (95% confidence interval CI, -0.6 to -0.3 mmHg) at 12 months and -0.4 mmHg (95% CI, -0.6 to -0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2-3.8; P = 0.012] and 2.1 [95% CI, 1.1-3.8; P = 0.025], respectively). CONCLUSIONS: Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk.

Four-week outcomes of vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration.

IMPORTANCE: To assess early outcomes of intravitreal vascular endothelial growth factor (VEGF) inhibitor treatment in neovascular age-related macular degeneration (nAMD) before patients have a chance to miss or discontinue treatment. BACKGROUND: Intravitreal VEGF inhibitors used to treat nAMD have been compared in various ways. The present study compared the 4-week responses to the first injection of either aflibercept, bevacizumab, or ranibizumab. DESIGN: Observational study. PARTICIPANTS: Treatment-naïve nAMD patients with visual acuity (VA) taken 22 to 48 days after the first treatment with an intravitreal VEGF inhibitor. METHODS: An observational study from a prospectively designed database. MAIN OUTCOME MEASURES: VA change from baseline and proportion of eyes judged active 22 to 48 days after the first treatment. RESULTS: The overall mean (95% confidence interval [CI]) VA change at 4 weeks was +3.7 (3.3, 4.0) letters. No pairwise comparisons in crude VA change or VA change after multivariate adjustment between the three agents were significant. However, after multivariate adjustment, more eyes treated with bevacizumab (90%) had active disease 4 weeks after the first injection than ranibizumab (84%; P = .013) and aflibercept (82%; P = .004). Older age, higher baseline vision and larger lesions were associated with lower VA change. CONCLUSION: There was no significant difference in VA gains amongst all three drugs but ranibizumab and aflibercept seemed to be more efficacious in quelling disease activity 4 weeks after the first treatment. VA change after the first injection was driven largely by baseline characteristics such as age, baseline VA and lesion size.

Changes in real-world treatment patterns for diabetic macular oedema from 2009 to 2019 and 5-year outcomes: Data from the Fight Retinal Blindness! Registry.

IMPORTANCE: Evaluating the treatment outcomes of diabetic macular oedema (DMO) in routine clinical practice provides data for comparison with those of clinical trials. BACKGROUND: Phase 3 clinical trials of vascular endothelial growth factor (VEGF) inhibitors for DMO have reported significant improvements in visual acuity (VA) not previously reported with laser and steroid treatments. DESIGN: Retrospective analysis of observational data from routine clinical practice. PARTICIPANTS: Eyes receiving treatments for DMO tracked in the Fight Retinal Blindness! Registry. METHODS: We analysed 510 eyes (347 patients) that started DMO treatment between 2009 and 2014. MAIN OUTCOME MEASURES: Changes in DMO treatment patterns and mean change in VA (letters logMAR) and central subfield thickness (CST) 5 years after starting treatment. RESULTS: Treatment choice for DMO changed to predominantly VEGF inhibitors from 2009 to 2014. A total of 238 eyes (47%) were followed for at least 5 years. The mean VA at the start of treatment improved from 2009 (58 letters) to 2014 (68 letters) while mean VA change at 5 years were + 4.5 and + 5.3 letters for eyes starting treatment in 2009 and 2014, respectively. The mean CST dropped from 401 µm at baseline to 314 µm at 5 years. Eyes received a median of four injections in the first, two in the second, third and fourth and three in the fifth years. CONCLUSIONS AND RELEVANCE: Changing the treatment of DMO from macular laser and intravitreal triamcinolone to VEGF inhibitors from 2011 onwards was associated with better VA outcomes, part of which were due to better VA at the start of treatment. The outcomes of treatment in eyes in real-world practice were, however, worse than those reported by clinical trials, likely because they were undertreated.

PREVALENCE AND RISK FACTORS FOR THE DEVELOPMENT OF PHYSICIAN-GRADED SUBRETINAL FIBROSIS IN EYES TREATED FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the prevalence and incidence of and risk factors for subretinal fibrosis (SRFi) in eyes with neovascular age-related macular degeneration (nAMD) that underwent vascular endothelial growth factor inhibitor treatment for up to 10 years. METHODS: A cross-sectional and longitudinal analysis was performed on data from a neovascular age-related macular degeneration registry. The presence and location of SRFi were graded by the treating practitioner. Visual acuity, lesion characteristics (type, morphology, and activity), and treatment administered at each visit was recorded. RESULTS: The prevalence of SRFi in 2,914 eyes rose from 20.4% at year interval 0-1 to 40.7% at year interval 9 to 10. The incidence in 1,950 eyes was 14.3% at baseline and 26.3% at 24 months. Independent characteristics associated with SRFi included poorer baseline vision (adjusted odds ratio 5.33 [95% confidence interval 4.66-7.61] for visual acuity ≤35 letters vs. visual acuity ≥70 letters, P < 0.01), baseline lesion size (adjusted odds ratio 1.08 [95% confidence interval 1.08-1.14] per 1000 µm, P = 0.03), lesion type (adjusted odds ratio 1.42 [95% confidence interval 1.17-1.72] for predominantly classic vs. occult lesions, P = 0.02), and proportion of active visits (adjusted odds ratio 1.58 [95% confidence interval 1.25-2.01] for the group with the highest level of activity vs. the lowest level of activity, P < 0.01). CONCLUSION: Subretinal fibrosis was found in 40% of eyes after 10 years of treatment. High rates of lesion activity, predominantly classic lesions, poor baseline vision, and larger lesion size seem to be independent risk factors for SRFi.