Treat-and-Extend Versus Pro re nata Regimens of Ranibizumab and Aflibercept in Neovascular Age-Related Macular Degeneration: A Comparative Study from Routine Clinical Practice.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or "treat-and-extend" (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. METHODS: We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. RESULTS: From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p < 0.001), with more injections (14.9 standard deviation(SD) 4.3) vs. 9.8(SD 4.3); p < 0.001). CONCLUSIONS: Eyes treated with a T&E regimen had better VA outcomes from VEGF inhibitors than eyes treated PRN. This large real-world data assessment supports previous data from randomized clinical trials that the T&E regimen delivers better outcomes than PRN.

This study focused on comparing two methods of treating neovascular age-related macular degeneration, a common eye condition. The treatments used were ranibizumab and aflibercept. We looked at the reactive "pro re nata" method, where treatment is given sporadically and only when the condition reactivates, and the proactive "treat-and-extend" method, which aims to keep the disease inactive with the fewest treatments at regular intervals. The main aim was to determine which method provides the best vision outcomes over a 24-month period and the frequency of treatment required. We found that the treat-and-extend method resulted in a greater improvement in vision than the pro re nata method, although it did require more injections. This study highlights the effectiveness of the treat-and-extend method for neovascular age-related macular degeneration, suggesting it gets better outcomes despite requiring more injections.

[Primary stromal cyst of the iris: case report].

Primary stromal cysts of the iris are rare, often asymptomatic, and incidentally found entities. Treatment is usually indicated in cases of enlargement or complications. However, imaging tests are required to determine their cystic nature and make an accurate differential diagnosis with malignant tumors, as well as for long-term follow-up. Ultrasound biomicroscopy is the technique of choice, although in most centers anterior segment optical coherence tomography is a more accessible and available imaging modality. We present a case of primary stromal cyst of the iris with an atypical presentation to illustrate the diagnosis and initial follow-up using anterior segment optical coherence tomography and photographs, and the management of complications. Anterior segment optical coherence tomography may be useful in the initial study and follow-up of anterior non-pigmented lesions where the cyst can be fully seen.

Biometric description of 34 589 eyes undergoing cataract surgery: sex differences.

PURPOSE: To describe gender differences in the biometric parameters of a large sample of patients with cataract. Cataract surgery has evolved from a vision restoration to a refractive procedure, and population-based studies are vital to optimize normative databases and postsurgical outcomes. SETTING: Miguel Servet University Hospital, Zaragoza, Spain. DESIGN: Retrospective single-center observational study. METHODS: The study included 34 589 eyes (20 004 patients with cataract). Biometric data were obtained from IOL Master 700 and Pentacam HR. Linear mixed models were used to account for intereye correlation. HofferQST formula was used to calculate the hypothetical distribution of intraocular lens (IOL) power (arbitrary lens; A = 119.2). RESULTS: Most biometric variables showed significant differences between sexes ( P < .0001), such as 0.53 mm shorter eyes found in females, of which 0.16 mm are explained by shorter aqueous depth. Steeper anterior keratometries (∼0.75 diopter [D]) were found in women, to end up in no difference on anterior astigmatism magnitude, but different orientation ( P < .0001). The distribution of IOL power differed between sexes ( P < .001), with the interquartile range shifting 1 D toward more powerful lenses in women and odds ratio (power >26 D) = 2.26, P < .0001 (Fisher). CONCLUSIONS: Large sample size studies provide smaller margin of error, higher power, and controlled risk of reporting false (negative or positive) findings. Highly significant differences between sexes in ocular biometry were found; this supports the idea that including sex as a parameter in IOL calculation should be explored and may improve results. In addition, the distribution of IOL powers was provided, which may be useful for manufacturers and hospital stock planning.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

OUTCOMES OF SWITCHING FROM PROACTIVE TO REACTIVE TREATMENT AFTER DEVELOPING ADVANCED CENTRAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We assessed outcomes of eyes with neovascular age-related macular degeneration (nAMD) that switched from proactive (treat-and-extend) to reactive (pro re nata) treatment regimen after developing macular atrophy (MA) or submacular fibrosis (SMFi). METHODS: Data were collected from a retrospective analysis of a prospectively designed, multinational registry of "real-world" nAMD treatment outcomes. Eyes without MA or SMFi when starting treatment with a vascular endothelial growth factor inhibitor regimen that subsequently developed MA or SMFi were included. RESULTS: Macular atrophy developed in 821 eyes and SMFi in 1,166 eyes. Seven percent of eyes that developed MA and 9% of those that developed SMFi were switched to reactive treatment. Vision was stable at 12 months for all eyes with MA and inactive SMFi. Active SMFi eyes that switched to reactive treatment had significant vision loss. No eyes that continued proactive treatment developed ≥15 letter loss, but 8% of all eyes that switched to a reactive regimen and 15% of active SMFi eyes did. CONCLUSION: Eyes that switch from proactive to reactive treatment after developing MA and inactive SMFi can have stable visual outcomes. Physicians should be aware of the risk of a significant loss of vision in eyes with active SMFi that switch to reactive treatment.

Subretinal fluid may protect against macular atrophy in neovascular age-related macular degeneration: 5 years of follow-up from Fight Retinal Blindness registry.

PURPOSE: The purpose of the study was to assess the association of macular atrophy (MA) according to the activity of macular neovascularization (MNV) (inactive, only subretinal fluid [SRFL], or active, i.e. including intraretinal fluid [IRFL]) using optical coherence tomography (OCT) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Multicentric observational study. Treatment-naïve nAMD eyes without subfoveal MA or subretinal fibrosis (SF) at baseline were included since 1st January 2010 and 30th September 2016 to allow up to 5 years of treatment follow-up. Eyes were grouped based on their predominant activity status as: (1) mostly inactive, (2) mostly active non-SRFL only [IRFL] or (3) mostly active-SRFL only [onlySRFL]. Kaplan-Meier survival curves estimated the time to development of MA or SF. Cox proportional hazards models evaluated predictors of developing subfoveal MA or SF. The main outcome measure was the risk of developing MA according to predominant MNV activity. RESULTS: A total of 973 eyes were eligible for analysis. OnlySRFL eyes had lower risk of developing subfoveal MA (HR [95% CI]: 0.56 [0.36, 0.88]; p = 0.024) and extrafoveal MA (HR [95% CI]: 0.41 [0.27, 0.61]; p < 0.001) than IRFL eyes. IRFL eyes had lower visual acuity (VA) (54.5 letters) and the highest proportion of eyes with vision ≤35 letters (25%) at 5 years while onlySRFL eyes had comparable 5-year VA (63.7 letters) to inactive eyes (63.7 letters). CONCLUSION: Subretinal fluid appears to protect against MA. Distinguishing the compartment of retinal fluid and understanding its relationship with MA and SF can guide the management of nAMD.

Creation of a neovascular age-related macular degeneration national database using a web-based platform: Fight Retinal Blindness Spain. Report 1: Visual outcomes.

BACKGROUND: To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level. METHODS: Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!). RESULTS: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%). CONCLUSION: Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts.

Ocular related emergencies in Spain during the COVID-19 pandemic, a multicenter study.

PURPOSE: To evaluate ophthalmological emergencies (OE) during the COVID-19 pandemic comparing them with the same period of the previous year. METHODS: Retrospective observational study of all OE visits in four tertiary hospitals in Spain comparing data from March 16th to April 30th, 2020 (COVID-19 period) and the same period of 2019 (pre-COVID-19 period). Severity of the conditions was assessed following Channa et al. publication. Data on demographics, diagnosis and treatments were collected from Electronic Medical Records. RESULTS: During lockdown, OE significantly declined by 75.18%, from 7,730 registered in the pre-COVID-19 period to 1,928 attended during the COVID-19 period (p < 0.001). In 2019, 23.86% of visits were classified as emergent, 59.50% as non-emergent, and 16.65% could not be determined. In 2020, the percentage of emergent visits increased up to 29.77%, non-emergent visits significantly decreased to 52.92% (p < 0.001), and 17.31% of the visits were classified as "could not determine". During the pandemic, people aged between 45 and 65 years old represented the largest attending group (37.89%), compared to 2019, where patients over 65 years were the majority (39.80%). In 2019, most frequent diagnosis was unspecified acute conjunctivitis (11.59%), followed by vitreous degeneration (6.47%), and punctate keratitis (5.86%). During the COVID-19 period, vitreous degeneration was the first cause for consultation (9.28%), followed by unspecified acute conjunctivitis (5.63%) and punctate keratitis (5.85%). CONCLUSIONS: OE visits dropped significantly during the pandemic in Spain (75.18%), although more than half were classified as non-urgent conditions, indicating a lack of understanding of the really emergent ocular pathologies among population.

ASSOCIATION BETWEEN ANATOMICAL AND CLINICAL OUTCOMES OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: Assess the relationship between subretinal fluid (SRFL), intraretinal fluid, and visual outcomes of neovascular age-related degeneration in routine clinical practice. METHODS: Treatment-naive eyes enrolled in the Fight Retinal Blindness! registry after January 2017 were identified. Lesion activity was graded at each visit as inactive, active not SRFL only (A-NSRFL only), or active SRFL only (A-SRFL only). Eyes were grouped based on initial activity as follows: 1) initially A-NSRFL only or 2) initially A-SRFL only, and their predominant activity status over 12 months was as follows: 1) mostly inactive, 2) mostly A-NSRFL only, or 3) mostly A-SRFL only. RESULTS: Seven hundred and three eyes were eligible for analysis. Initially A-NSRFL only had a similar adjusted mean 12-month visual acuity change to initially A-SRFL eyes (5.7 vs. 6.9 letters; P = 0.165), but their final visual acuity was worse (62.5 vs. 67.5 letters at 12 months; P = 0.003). The adjusted mean 12-month visual acuity change between the predominant activity groups was significantly different (P = 0.005), with mostly inactive (7.6 letters) and mostly A-SRFL only (7.5 letters) eyes gaining more than mostly A-NSRFL only eyes (3.6 letters). CONCLUSION: Eyes with SRFL only had similar outcomes at 1 year to eyes that were mostly inactive. Intraretinal fluid was associated with worse visual outcomes, highlighting the importance of distinguishing between intraretinal fluid and SRFL when managing neovascular age-related degeneration.