Effect of intravitreal injections due to neovascular age-related macular degeneration on retinal nerve fiber layer thickness and minimum rim width: a cross sectional study.

PURPOSE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head. PATIENTS AND METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). RESULTS: Mean global RNFL was 90.62 µm and both RNFL as well as MRW significantly decreased with advanced age (p = 0.005 and p = 0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p = 0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p = 0.012). The same holds true when adjusted for the confounding factor age (RNFL p = 0.566 and MRW p = 0.023). CONCLUSION: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.

Relative yield of retinal imaging versus clinical exam in following neovascular exudative age related macular degeneration.

PURPOSE: To compare therapeutic decisions between 3 diagnostic protocols and to assess the need for in-person physical doctor-patient encounter in follow up and treatment of neovascular exudative age-related macular degeneration (AMD). METHODS: Analysis of 88 eyes of 88 unique patients with neovascular AMD who were routinely followed at our medical retina clinic. A retinal specialist reviewed all images in advance and wrote his decisions. He later attended an in-person encounters with all patients and documented his decisions. Masking was done by not exposing any identifying information to the specialist and by randomizing patient's images order before the in-person encounter. Therapeutic decisions regarding intravitreal injections intervals and agent selection were made based on three protocols: (1) optic coherence tomography (OCT); (2) OCT/Ultra-widefield (UWF) color image; (3) OCT/UWF/full clinical exam. Visual acuity (VA) was incorporated into all protocols. RESULTS: We found an agreement of 93% between those protocols regarding the intervals of injections, and of 100% regarding injection agent selection. When comparing OCT, OCT/UWF and OCT/UWF/clinical exam guided decision making, there were no discrepancies between OCT and OCT/UWF. There were 6 out of 88 discrepancies (7%) between OCT/UWF and OCT/UWF/clinical exam. Of those 6 discrepancies, all were regarding intervals (Bland-Altman bias = - 0.2386). All discrepancies between OCT/UWF and OCT/UWF/Clinical exam were due to patients' preferences, socioeconomic issues and fellow eye considerations, addressed during the face-to-face encounter with patients. Physical examination itself did not affect decision making. CONCLUSIONS: Neovascular exudative AMD follow up and treatment decisions can be guided by VA and OCT, with UWF adding important information regarding macula and peripheral retina, but rarely affecting decision making. However, decision making may also be driven by patients' preferences and other considerations that are being made only during the face-to-face visit and discussion. Thus, every approach supporting imaging only decision making, must take these factors into account.

Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).

BACKGROUND: The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes. PATIENTS AND METHODS: This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations. RESULTS: Mean patient age was 80.5 ± 6.2 years. The mean length of total follow-up was 39.7 ± 13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8 ± 355.5 µm from the first consultation to 562.8 ± 251.5 µm at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p = 0.004, n = 14). The mean visual acuity before rupture was 66.2 ± 16.0 letters. Mean visual acuity deteriorated to 60.8 ± 18.6 letters at the first consultation after rupture (p = 0.052, n = 21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5 ± 23.7 ETDRS letters (p = 0.23, n = 19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35 ± 2.94 mm2 (baseline) to 6.81 ± 6.25 mm2 over the course of 2 years (p = 0.000 013, n = 20). CONCLUSIONS: The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.

Relationship of Topographic Distribution of Macular Atrophy Secondary to Neovascular AMD and Reading Performance.

Purpose: The purpose of this study was to provide a topographical assessment of macular atrophy in successfully treated neovascular age-related macular degeneration (AMD) eyes to investigate determinants of monocular reading performance. Methods: A total of 60 participants (60 eyes) with previously treated neovascular AMD and absence of optical coherence tomography (OCT) signs of exudation were enrolled. Reading performance was assessed monocularly using Radner charts. The following variables were obtained: (i) the reading acuity was defined as the logarithm of the reading acuity determination (LogRAD), at the smallest sentence, a patient is able to read in less than 30 seconds; (ii) the maximum reading speed was defined as the fastest time achieved and is calculated in words per minute (wpm). OCT images were reviewed for the presence of macular atrophy within the central, 4 inner and 4 outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid subfields. Contributory factors affecting reading performance were examined using univariable and multivariable linear mixed model considering reading acuity and reading speed as dependent variables. Results: Median (interquartile range [IQR]) values were 0.53 (IQR = 0.17) LogRAD for reading acuity, and 144 (60) wpm for maximum reading speed. Thirty-five out of 60 (58.3%) eyes were characterized by the presence of macular atrophy. In multiple regression analysis, reading acuity was significantly associated with presence of macular atrophy in the foveal central circle (P = 0.024). Conversely, the maximum reading speed was associated with presence of macular atrophy in the inner-right ETDRS subfield (P = 0.005). Conclusions: We showed a significant relationship between presence and location of macular atrophy and reading performance in neovascular AMD.

A concentrated machine learning-based classification system for age-related macular degeneration (AMD) diagnosis using fundus images.

The increase in eye disorders among older individuals has raised concerns, necessitating early detection through regular eye examinations. Age-related macular degeneration (AMD), a prevalent condition in individuals over 45, is a leading cause of vision impairment in the elderly. This paper presents a comprehensive computer-aided diagnosis (CAD) framework to categorize fundus images into geographic atrophy (GA), intermediate AMD, normal, and wet AMD categories. This is crucial for early detection and precise diagnosis of age-related macular degeneration (AMD), enabling timely intervention and personalized treatment strategies. We have developed a novel system that extracts both local and global appearance markers from fundus images. These markers are obtained from the entire retina and iso-regions aligned with the optical disc. Applying weighted majority voting on the best classifiers improves performance, resulting in an accuracy of 96.85%, sensitivity of 93.72%, specificity of 97.89%, precision of 93.86%, F1 of 93.72%, ROC of 95.85%, balanced accuracy of 95.81%, and weighted sum of 95.38%. This system not only achieves high accuracy but also provides a detailed assessment of the severity of each retinal region. This approach ensures that the final diagnosis aligns with the physician's understanding of AMD, aiding them in ongoing treatment and follow-up for AMD patients.

One-year results of treat-and-extend regimen with intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To evaluate 1-year outcomes of loading phase treatment followed by maintenance therapy using a treat-and-extend (TAE) regimen with intravitreal faricimab for neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective, interventional case series. METHODS: We retrospectively studied 40 eyes of 38 consecutive patients with treatment-naïve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit. RESULTS: Thirty eyes (75.0%) had completed the 1-year intravitreal faricimab treatment. Their BCVA showed significant improvement, with significant reductions in foveal thickness and CCT. The total number of injections during the 1-year treatment period was 6.6 ± 0.7. The intended injection interval at the last visit was 12.7 ± 3.3 weeks. Of the 10 eyes (25.0%) failing to complete the 1-year faricimab treatment, 1 eye developed intraocular inflammation after the loading phase treatment but showed no recurrence of exudative changes, and no further treatment was required. Moreover, 5 eyes switched to intravitreal brolucizumab injection due to persistent exudative changes with an 8-week interval of faricimab injections. The remaining 4 eyes either dropped out or the patient died. CONCLUSIONS: A loading phase treatment followed by a TAE regimen with intravitreal faricimab appears to be generally safe and effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of faricimab every 8 weeks in the maintenance phase.

ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed. RESULTS: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g. CONCLUSION: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.

Age-Related Macular Degeneration: A Review.

Importance: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040. Observations: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment. Conclusions and Relevance: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.

Structural and clinical changes in previously treated type 1 macular neovascularization in non-responder AMD eyes switched to brolucizumab.

PURPOSE: To examine structural and clinical changes in previously treated type 1 macular neovascularization (MNV) in non-responder age-related macular degeneration (nAMD) eyes switched to brolucizumab. Subretinal hyper-reflective material (SHRM), intraretinal (IRF) and subretinal fluid (SRF) presence, fibrovascular-pigment epithelium detachment (PED) height and central macular thickness (CMT) variation were analyzed using optical coherence tomography (OCT). METHODS: In this prospective study all patients underwent a complete ophthalmological evaluation including structural OCT at baseline (T0), one month (T1), three (T2), four (T3) and six months after switching to brolucizumab treatment (T4). Non-responder criterion was the persistence of IRF and SRF. Moreover, CMT and BCVA had shown worsening or no improvement before switching to brolucizumab. Clinical function and structural activity biomarkers were measured at each visit and changes were analyzed. P value <0.05 was considered statistically significant. RESULTS: Twenty eyes of twenty patients were enrolled. All the structural variables examined during the follow-up showed significant reductions. Decreases in IRF, SRF and PED were already significant at T1 (p < 0.05). SHRM was significantly reduced at T2 (p < 0.05). Structural biomarkers were absent at T3. At T4, all biomarkers remained stable while SHRM was no longer detectable in 18 patients. Changes in visual acuity from baseline to T4 were not significant. CONCLUSION: This short-term experience highlights that brolucizumab might be considered an effective treatment option in nAMD with type 1 MNV, as it can promote a reduction of structural activity biomarkers.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

Retinal vascular structure independently predicts the initial treatment response in neovascular age-related macular degeneration.

PURPOSE: Prediction of the early treatment response is important in neovascular age-related macular degeneration (nAMD). Hence, we aimed to test if non-invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. METHODS: In 58 eyes of 58 patients with treatment-naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra- or subretinal fluid or macular haemorrhage. RESULTS: Of 54 eyes attending follow-up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length-diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82-0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68-1.00, p = 0.05, for each 0.01 unit increment). CONCLUSION: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long-term, prospective studies, this might help to guide treatment.

LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.

Association between Oral Active-Matrix Metalloproteinase-8 Levels and Subretinal Fibrosis among Wet Age-Related Macular Degeneration Patients.

PURPOSE: Periodontitis causes low-grade systemic inflammation and has been associated with elevated active-matrix metalloproteinase (aMMP-8) levels, blood-ocular barrier breakdown and a risk of wet age-related macular degeneration. To assess the association between aMMP-8 levels and macular status among patients with wet age-related macular degeneration (AMD). METHODS: Patients on anti-VEGF treatment for wet AMD were enrolled for oral aMMP-8 rinse test in Mehiläinen Private Hospital, Helsinki, Finland. Macular status was examined from spectral-domain optical coherence tomography (SD-OCT) scans by a medical retina specialist and aMMP-8 levels were analyzed with chairside point-of-care oral rinse (PerioSafe®) test and real-time quantitated by a dentist using the ORALyzer®- reader with a 10 ng/ml cut-off for aMMP-8 activity. RESULTS: Elevated aMMP-8 levels were found in 10 out of 32 patients. Age, gender, anti-VEGF (bevacizumab or aflibercept) distribution, cumulative number of anti-VEGF injections and treatment interval were comparable between patients with aMMP-8 levels below and above the point-of-care level. Macular status differed in regard to aMMP-8 activity; among patients with aMMP-8 levels below the point-of-care subretinal fibrosis was found in 6 out of 22 eyes, whereas among patients with aMMP-8 levels above the point-of-care subretinal fibrosis was found in 8 out of 10 eyes (p = 0.005). Respectively, the mean thickness of subretinal fibrosis at fovea was 19.5 ± 44.1 and 92.3 ± 78.3 µm (p = 0.018). No differences were found in the presence and in the area of geographic atrophy, or fluid distribution, whereas thicknesses of serous pigment epithelial detachment (65.5 ± 99.5 and 12.9 ± 27.9 µm, p = 0.038) and neuroretina (204.2 ± 57.8 µm and 143.0 ± 43.7 µm, p = 0.006) were greater in the eyes of patients with physiological aMMP-8 levels compared to those with elevated aMMP-8 levels. CONCLUSION: Elevated aMMP-8 levels may account for subretinal fibrosis formation in wet AMD.

ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans. METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories. RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021). CONCLUSION: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.

Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up).

PURPOSE: To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space). METHODS: This retrospective study included 58 eyes from 53 patients with naïve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections. RESULTS: Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210 ± 45 µm vs 191 ± 52 µm, p = 0.01) before treatment and (170 ± 47 µm vs 179 ± 48 µm, p = 0.24) after 60 months. BCVA (log MAR) in group 1 vs group 2 was (0.57 ± 0.18 vs 0.53 ± 0.22, p = 0.47) before treatment and (0.59 ± 0.23 vs 0.69 ± 0.16, p = 0.04) after 60 months. CMT in group 1 vs group 2 was (398 ± 154 µm vs 382 ± 103 µm, p = 0.86) before treatment and (297 ± 68 µm vs 283 ± 67 µm, p = 0.14) after 60 months. The number of injections per eye over a period of 60 months was significantly higher in group 1 (34.9 ± 11 vs 29.0 ± 14, p = 0.04). The proportion of eyes with subfoveal GA after 60 months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p = 0.03). CONCLUSION: Over the full 60 months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.

Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.

PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified. CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

Changes in the uninjected contralateral eye after intravitreal brolucizumab for exudative age-related macular degeneration.

PURPOSE: Herein we describe the change in the amount of macular oedema in one eye after contralateral intravitreal brolucizumab injections in a patient with neovascular age-related macular degeneration (nAMD). CASE REPORT: A patient with bilateral nAMD underwent intravitreal bevacizumab injections in both eyes with little improvement in the best-corrected visual acuity (BCVA) and central macular exudation. The treatment was switched to aflibercept, but there was incomplete drying of the macula in both eyes. After uneventful cataract extraction, the central macular thickness (CMT) increased markedly in the operated left eye (LE), which was unresponsive to subtenon triamcinolone and further intravitreal aflibercept. Cataract surgery was also performed in the right eye (RE) combined with an intravitreal sustained-release dexamethasone implant. Nevertheless, the CMT increased. Intravitreal brolucizumab injections were performed in the RE with almost complete disappearance of the oedema in the treated eye. Concurrently, the contralateral uninjected eye showed a remarkable decrease in CMT. Five months after the first brolucizumab injection, the macular exudation increased again in both eyes. A second brolucizumab injection was performed in the RE only, and was followed by a prompt reduction in CMT in both the injected RE and uninjected LE. CONCLUSIONS: Although contralateral retinal changes have been described for many other vascular endothelial growth factor inhibitors, there is little evidence for brolucizumab. We describe a repeated dose- and time-related effect on the uninjected eye in a case of nAMD.

Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.

PURPOSE: To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. METHODS: In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. RESULTS: The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). CONCLUSION: Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.

Incidence and multimodal imaging characteristics of macular neovascularisation subtypes in Chinese neovascular age-related macular degeneration patients.

AIMS: To investigate the incidence of macular neovascularisation (MNV) subtypes of neovascular age-related macular degeneration (nAMD) and summarise these subtypes' clinical features in the Chinese population using multimodal imaging. METHODS: We retrospectively analysed 506 consecutive treatment-naïve nAMD patients (582 eyes). Incidence of MNV subtypes and clinical features were recorded based on their multimodal images. The classification of MNV subtypes in nAMD patients were referred to Consensus on Neovascular Age-related Macular Degeneration Nonmenclature (CONAN) study group classifications. RESULTS: 460 eyes of 389 nAMD patients were included in our study. 68.5% (315/460) of nAMD eyes were from male. According to CONAN, we identified type 1 macular neovascularisation (MNV) in 61.1% of eyes (281/460), type 2 MNV in 16.3% of eyes (75/460), type 3 MNV in 2.0% of eyes (9/460), mixed type 1 and type 2 MNV in 20.6% of eyes (95/460). 58% of eyes (267/460) were diagnosed as polypoidal choroidal vasculopathy lesions (PCV). 45.2% of eyes (208/460) with PCV lesions were type 1 MNV and 12.8% of eyes (59/460) with PCV lesions were co-occurred with type 2 MNV. CONCLUSION: Based on the consensus anatomical classification system developed by the CONAN Study Group, we updated the incidence of MNV subtypes and found that PCV was the most common subtype and type 3 MNV was the least common subtype among Chinese nAMD patients. In addition, the co-occurrence of PCV and type 2 MNV was typically observed, and its frequency was reported in our study.