FEATURED ARTICLE
Faricimab in neovascular AMD: first report of real-world outcomes in an independent retina clinic.
Eye (London, England) 2023 Mar 23.
Stanga PE, Valentín-Bravo FJ, Stanga SEF, Reinstein UI, Pastor-Idoate S, Downes SM.
Purpose: Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab.
Methods: Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-naïve patients and non-naïve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded.
Results: Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612 ± 0.75 logMAR and 256.16 ± 12.98 µm respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387 ± 0.54 logMAR, as well as CRT values which decreased to 245.43 ± 15.34 µm. In the 3 naïve patients, mean baseline BVCA and CRT values were 0.33 ± 0.29 and 874.67 ± 510.86 µm, respectively. At one month follow-up, mean BCVA improved to 0.30 ± 0.29 logMAR and mean CRT was 536.04 ± 36.15 µm. Overall, a significant improvement in BCVA of 0.21 ± 41 logMAR and 238.44 ± 114.9 µm was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed.
Conclusion: Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.
DOI: 10.1038/s41433-023-02505-z
DRUG TREATMENT
Outcomes in patients with retinal vein occlusion with good baseline visual acuity.
Eye (London, England) 2023 Mar 22.
Liu JC, Vatti T, Seth K, Valentim CCS, Rachitskaya AV, Singh RP.
Background: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) are first-line therapy for macular oedema in retinal vein occlusion (RVO). Appropriate management for RVO with good visual acuity at diagnosis has not been evaluated. The purpose of this study is to analyse the visual and anatomic outcomes from anti-VEGF treatment among RVO patients with good vision at baseline.
Methods: This retrospective cohort study evaluated patients diagnosed with macular oedema secondary to RVO from January 2012 to February 2021 at a tertiary ophthalmic centre. Patients had a Snellen acuity of 20/32 or better at diagnosis. Three cohorts were compared: patients with no anti-VEGF treatment, delayed anti-VEGF treatment (initial injection >30 days post-diagnosis) and immediate anti-VEGF treatment (initial injection ≤30 days post-diagnosis). Central subfield thickness (CST) and best visual acuity (BVA) were collected at diagnosis and 6-, 12- and 24-month follow-up appointments.
Results: Among 131 eyes, mean BVA values among treatment groups did not differ at 6-, 12- or 24-month follow up visits (P = 0.521, 0.426, 0.356, respectively). The percentage of eyes with at least a 5-letter BVA decrease at 24 months was 24.1%, 65.0% and 30.8% in the no treatment, delayed and immediate treatment groups respectively (P = 0.010). There was no significant difference in the percentage of eyes with at least a 10% decrease in CST at 24 months among groups (P = 0.095).
Conclusions: Close observation with initiation of treatment in patients with good visual acuity with macular oedema secondary to RVO as indicated has similar outcomes in the setting of routine clinical practice.
DOI: 10.1038/s41433-023-02488-x
Evaluation of care with intravitreal aflibercept treatment for UK patients with diabetic macular oedema: DRAKO study 24-month real-world outcomes.
Eye (London, England). 2023 Mar 20.
Sivaprasad S, Ghanchi F, Kelly SP, Kotagiri A, Talks J, Scanlon P, McGoey H, Nolan A, Saddiq M, Napier J.
Background/ Objectives: DRAKO (NCT02850263) was a 24-month, prospective, observational, multi-centre cohort study that enrolled patients diagnosed with diabetic macular oedema (DMO) including central involvement. The study aimed to evaluate standard of care intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the 12-month outcomes for patients with prior anti-vascular endothelial growth factor (VEGF) treatment for DMO other than IVT-AFL (C2), and 2-year outcomes for both anti-VEGF treatment-naïve patients (C1) and C2 patients.
Methods: Study eyes were treated with IVT-AFL as per local standard of care. Mean changes in best-corrected visual acuity (BCVA) in ETDRS letters and central subfield thickness (CST) were stratified by baseline factors. Changes in diabetic retinopathy assessments, glycated haemoglobin A1c levels and vision-related quality of life (QoL) were evaluated alongside numbers of injections administered and safety outcomes.
Results: For C1, mean (SD) changes from baseline in BCVA of +0.7 (12.7) letters and CST of -123.3 (104.3) µm were observed at Month 24. For C2, mean (SD) changes from baseline for BCVA of + 0.2 (10.2) letters and -0.3 (13.0) letters, and CST of -79.1 (137.6) µm and -91.6 (132.9) µm, were observed at 12 and 24 months, respectively. In Year 2, C1 and C2 patients received a mean of 3.7 and 4.3 injections, respectively.
Conclusions: Year 2 results indicate that IVT-AFL is an effective treatment for DMO in real-world UK clinical practice, despite relatively low injection numbers. The high baseline visual acuity and QoL scores were maintained and there was further improvement in anatomical outcomes.
DOI: 10.1038/s41433-023-02409-y
RISK OF DISEASE
Posterior Vitreous Detachment and Its Role in the Evolution of Dry to Wet Age Related Macular Degeneration.
Clinical Ophthalmology (Auckland, N.Z.) 2023 Mar 17;
Bakaliou A, Georgakopoulos C, Tsilimbaris M, Farmakakis N.
Purpose: To examine the state of the posterior vitreous in eyes with exudative age-related macular degeneration, AMD, non-exudative AMD and in normal eyes. STUDY: This is a prospective, cross-sectional study.
Methods: B-scan ultrasonography and Optical Coherence Tomography, OCT were performed in 165 patients older than 65 years with any AMD and in 22 patients older than 65 years with normal eyes in order to diagnose the eyes with complete posterior vitreous detachment, PVD and the eyes with persistent central vitreomacular adhesion, VMA. All patients were selected from the outpatient clinic of the Ophthalmology Department in the University Hospital of Patras. Fundus Fluoroangiography, FFA was used in order to determine the development of exudative AMD from non-exudative AMD. Follow up time was 48 months. RESULTS: 16/171 eyes with exudative AMD (9.36%) had complete PVD, and the rest 155/171 (90.64%) had central VMA. Eleven of 138 eyes with non-exudative AMD (7.97%) had complete PVD and the remaining 127 eyes (92.03%) had central VMA. During the 48 months of the study, 28 eyes, all with central VMA progressed to exudative AMD.
Conclusion: Vitreomacular adhesion is associated with both exudative and non-exudative AMD. Progression of the non-exudative eyes to exudative AMD seems to be lower in eyes with complete PVD. On the other hand, the progression of normal eyes to exudative AMD appears to be independent of the posterior vitreous status. Larger and longer studies need to replicate these findings and support the potential of a protective role of complete posterior vitreous detachment in the evolution of the disease.
DOI: 10.2147/OPTH.S403242
DIAGNOSIS AND IMAGING
Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease.
Ophthalmology science 2023 Jan 31;
Akrobetu DY, Robbins CB, Ma JP, Soundararajan S, Quist MS, Stinnett SS, Moore KPL, Johnson KG, Liu AJ, Grewal DS, Fekrat S.
Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer’s disease (AD), mild cognitive impairment (MCI), Parkinson’s disease (PD), and normal cognition (NC).
Design: Cross sectional study.
Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis.
Methods Intervention Or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay.
Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging.
Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49-0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67-0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease.
Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability.
Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.
DOI: 10.1016/j.xops.2023.100275
Association Between Retinal Features from Multimodal Imaging and Schizophrenia.
JAMA Psychiatry 2023 Mar 22:
Wagner SK, Cortina-Borja M, Silverstein SM, Zhou Y, Romero-Bascones D, Struyven RR, Trucco E, Mookiah MRK, MacGillivray T, Hogg S, Liu T, Williamson DJ, Pontikos N, Patel PJ, Balaskas K, Alexander DC, Stuart KV, Khawaja AP, Denniston AK, Rahi JS, Petzold A, Keane PA.
Importance: The potential association of schizophrenia with distinct retinal changes is of clinical interest but has been challenging to investigate because of a lack of sufficiently large and detailed cohorts.
Objective: To investigate the association between retinal biomarkers from multimodal imaging (oculomics) and schizophrenia in a large real-world population.
Design, Setting, and Participants: This cross-sectional analysis used data from a retrospective cohort of 154 830 patients 40 years and older from the AlzEye study, which linked ophthalmic data with hospital admission data across England. Patients attended Moorfields Eye Hospital, a secondary care ophthalmic hospital with a principal central site, 4 district hubs, and 5 satellite clinics in and around London, United Kingdom, and had retinal imaging during the study period (January 2008 and April 2018). Data were analyzed from January 2022 to July 2022.
Main Outcomes and Measures: Retinovascular and optic nerve indices were computed from color fundus photography. Macular retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (mGC-IPL) thicknesses were extracted from optical coherence tomography. Linear mixed-effects models were used to examine the association between schizophrenia and retinal biomarkers.
Results: A total of 485 individuals (747 eyes) with schizophrenia (mean [SD] age, 64.9 years [12.2]; 258 [53.2%] female) and 100 931 individuals (165 400 eyes) without schizophrenia (mean age, 65.9 years [13.7]; 53 253 [52.8%] female) were included after images underwent quality control and potentially confounding conditions were excluded. Individuals with schizophrenia were more likely to have hypertension (407 [83.9%] vs 49 971 [48.0%]) and diabetes (364 [75.1%] vs 28 762 [27.6%]). The schizophrenia group had thinner mGC-IPL (-4.05 μm, 95% CI, -5.40 to -2.69; P = 5.4 × 10-9), which persisted when investigating only patients without diabetes (-3.99 μm; 95% CI, -6.67 to -1.30; P = .004) or just those 55 years and younger (-2.90 μm; 95% CI, -5.55 to -0.24; P = .03). On adjusted analysis, retinal fractal dimension among vascular variables was reduced in individuals with schizophrenia (-0.14 units; 95% CI, -0.22 to -0.05; P = .001), although this was not present when excluding patients with diabetes.
Conclusions and Relevance: In this study, patients with schizophrenia had measurable differences in neural and vascular integrity of the retina. Differences in retinal vasculature were mostly secondary to the higher prevalence of diabetes and hypertension in patients with schizophrenia. The role of retinal features as adjunct outcomes in patients with schizophrenia warrants further investigation.
DOI: 10.1001/jamapsychiatry.2023.0171
PATHOPHYSIOLOGY
Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.
Investigative ophthalmology & visual science. 2023 Mar 1;
Yoon CK, Kim YA, Park UC, Kwon SH, Lee Y, Yoo HJ, Seo JH, Yu HG.
Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics.
Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0.
Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment.
Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.
DOI: 10.1167/iovs.64.3.28
Serum miRNA modulations indicate changes in retinal morphology.
Frontiers in molecular neuroscience 2023 Mar 3;
Aggio-Bruce R, Schumann U, Cioanca AV, Chen FK, McLenachan S, Heath Jeffery RC, Das S, Natoli R.
Background: Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.
Methods: Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.
Results: Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.
Conclusion: In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.
DOI: 10.3389/fnmol.2023.1130249
REVIEWS
Identifying geographic atrophy.
Current opinion in ophthalmology. 2023 Mar 20.
Clevenger L, Rachitskaya A.
Purpose Of Review: Age-related macular degeneration (AMD) is one of the leading causes of blindness and can progress to geographic atrophy (GA) in late stages of disease. This review article highlights recent literature which assists in the accurate and timely identification of GA, and monitoring of GA progression.
Recent Findings: Technology for diagnosing and monitoring GA has made significant advances in recent years, particularly regarding the use of optical coherence tomography (OCT). Identification of imaging features which may herald the development of GA or its progression is critical. Deep learning applications for OCT in AMD have shown promising growth over the past several years, but more prospective studies are needed to demonstrate generalizability and clinical utility.
Summary: Identification of GA and of risk factors for GA development or progression is essential when counseling AMD patients and discussing prognosis. With new therapies on the horizon for the treatment of GA, identification of risk factors for the development and progression of GA will become critical in determining the patients who would be appropriate candidates for new targeted therapies.
DOI: 10.1097/ICU.0000000000000952
