CHARACTERIZING COVID-19-RELATED RETINAL VASCULAR OCCLUSIONS: A Case Series and Review of the Literature.

PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.

Remote screening of retinal and optic disc diseases using handheld nonmydriatic cameras in programmed routine occupational health checkups onsite at work centers.

PURPOSE: To evaluate the first year outcomes of a remote screening program for detection of retinal diseases using handheld nonmydriatic cameras in occupational routine checkups performed onsite at work centers. METHODS: Cross-sectional, first year screening program outcomes audit. Participants were volunteers recruited from staff within work centers. Retinal fundus images were captured by technicians, and images and data were anonymized and sent securely to a remote server. A team of ophthalmologists, all retinal specialists, remotely read the images using a custom-made software and sent telematic reports of findings within 24-48 h. The main items evaluated were the detection of retinal abnormalities and the relationship between retinal findings and demographic data such as age and sex. RESULTS: A total of 19,881 workers were evaluated in 52 centers. Mean age was 41.1 years old, 43.9% men and 56.1% women. Mean duration of the test was around 2 min. Of the workers, 7.8% presented abnormalities in retinal fundus images, being the main findings choroidal nevus (2.4%), macular pigment abnormalities (1.5%), glaucomatous optic disc (1.2%), and macular signs of high myopia (1.1%). The presence of abnormalities was associated with greater age, being 5%, 7.9%, 12.6%, and 19.7% in workers less than 40 years, from 40 to 49, 50-59, and ≥ 60 years (p < 0.05), respectively. Men had more abnormalities in retinal fundus images than women (8.6 vs. 7.2; p < 0.05 RR: 1.2; CI 1092-1322). CONCLUSIONS: Mass screening of retinal and optic disc abnormalities during occupational health routine checkups is a feasible, quick, and efficient tool for early detection of potential vision-threatening disease markers.

Prevalence of age-related macular degeneration among optometric telemedicine users in Spain: a retrospective nationwide population-based study.

PURPOSE: To evaluate the prevalence of AMD among optometric telemedicine users in Spain and to identify risk factors. METHODS: Retrospective analysis of a nationwide database conducted on subjects attending to optometry centers, between January 2013 and December 2019. Fundus photographs were performed by optometrists, using non-mydriatic cameras, and evaluated by a group of 12 retina specialists. RESULTS: Among the 119,877 subjects included, the overall prevalence of AMD was 7.6%. The prevalence of early, intermediate, and advanced AMD was 2.9%, 2.7%, and 2.0%, respectively. Of the 9129 AMD subjects, 1161 (12.7%) had geographic atrophy, and 1089 (11.9%) had neovascular AMD, either scar (4.5%) or exudative (7.4%). There was a significant association between AMD and age (per year older, adjusted odds ratio, OR 1.116; 95% CI 1.114 to 1.119, p<0.0001). Women had higher prevalence (adjusted OR 1.17; 95% CI 1.12 to 1.23, p<0.0001). Every diopter (spherical equivalent) of progress toward hyperopia was associated with a significant increase in early AMD prevalence (adjusted OR 1.02, 95 CI 1.01 to 1.04, p=0.0074). Presence of diabetes was associated with a lower AMD prevalence (p<0.0001). CONCLUSIONS: The prevalence of AMD (any eye and any severity) was 7.6%, with a prevalence of advanced AMD of 2.0%. Older age and women were significantly associated with a higher prevalence of AMD, whereas myopia and presence of diabetes were associated with significantly lower odds of any AMD.

Economic burden of age-related macular degeneration in routine clinical practice: the RAMDEBURS study.

PURPOSE: To describe and evaluate the main direct health costs, in routine clinical practice, of age-related macular degeneration (AMD) patients, from hospital perspective, in Spain. METHODS: Retrospective, multicenter, and observational study conducted on five third-level Spanish hospitals, between December 2018 and December 2019. The study included patients who were diagnosed of AMD before December 2018. Direct healthcare costs were obtained from a Spanish database. Study variables included demographic and clinical variables, and resources, such as treatment, diagnostic tests, medical examination, and surgery. Among the 1414 screened AMD patients, 1164 patients were included. In the overall study patients, the total cost was €5,386,511.0, with a mean cost per patient of €4627.6 ± 2383.9. The largest cost items were diagnostic examinations (€2.832.902,0) and vascular endothelial growth factor inhibitors (anti-VEGF) treatment (€2.038.257,2). Bevacizumab was administered to 325 (27.9%) patients, ranibizumab to 328 (28.2%), and aflibercept to 626 (53.8%); 115 (10.7%) patients received two anti-VEGF treatments, while 90 (7.7%) did not receive any. Over the course of the study, a total of 6,057 anti-VEGF injections were administered, with a mean (95% confidence interval) of 4.8 (4.4-5.2) injections per patient. Regarding safety, 29 patients experience injection-related adverse events, among them 12 patients had cataract and 11 ones elevated intraocular pressure (IOP). The incidence of endophthalmitis was 0.5% (6/1164). CONCLUSIONS: AMD was associated with considerable healthcare costs for regional healthcare systems. Diagnostic examinations, particularly OCT examinations, and anti-VEGF treatment represented the largest cost items.

Age and gender influence on foveal avascular zone in healthy eyes.

The foveal avascular zone (FAZ) is the capillary-free area in the central macula with high photoreceptor density and metabolic activity. In the present study we measured the superficial and deep macular foveal avascular zone (sFAZ, dFAZ) in the eyes of healthy adults of both sexes of various ages ranging from 10 to 69 years using optical coherence tomography angiography (OCT-A) in order to evaluate the influence of gender and age on FAZ size. A cross-sectional study was carried out in 240 eyes of 120 healthy subjects, OCT-A was performed by means of a Topcon swept source OCT. sFAZ and dFAZ areas were measured using the IMAGEnet6 software package. Subjects were grouped by age (six groups) and gender. The mean ±â€¯sd age of the subjects was 39.2 ±â€¯17.4 years (50% women, 50% men), ranging from 10 to 69 years. The overall mean sFAZ size in women (0.297 ±â€¯0.110 mm2) was significantly larger (p = 0.002) than in men (0.254 ±â€¯0.098 mm2). Similarly, the overall mean dFAZ in women (0.322 ±â€¯0.111 mm2) was significantly larger (p < 0.001) than in men (0.273 ±â€¯0.099). However, when analyzed by age group, these gender differences appeared only in groups younger than 20 years old and older than 50 years old. Men did not show differences among the six age groups. In women, for both sFAZ and dFAZ, the 20-29 year old group had a smaller FAZ size than the 50-59 year old group. In conclusion for both sFAZ and dFAZ, women have larger areas than men, but this occurs only in the young and old age groups. In men, age does not seem to influence the size of the FAZ, but in women, both sFAZ and dFAZ were significantly smaller in younger than in older ages. These results suggest that retinal changes in retinal structure caused by aging may be different in woman than in men, probably reflecting the more hormonal variations known to exist with age in women.

ULTRASONOGRAPHIC FINDINGS IN THE VITREOUS OF PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS.

PURPOSE: We aimed to assess the relationship of repeated intravitreal injection of anti-vascular endothelial growth factor, the main treatment for exudative age-related macular degeneration, with changes in vitreous ultrasonographic findings in patients with age-related macular degeneration. METHODS: We retrospectively collected data from 41 patients (41 age-related macular degeneration eyes, 41 control eyes) on age, sex, number of injections, and type of anti-vascular endothelial growth factor (ranibizumab, aflibercept). Ocular ultrasonography was performed with open eyelids, under topical anesthesia, and using carbomers as ultrasonographic gel. Topographic, quantitative, and kinetic ultrasonography was performed in all eye quadrants using a 10-MHz posterior pole probe, and vitreous reflectivity was assessed. RESULTS: The mean age of patients was 79 (range: 59-94) years, with a mean of five intravitreal anti-vascular endothelial growth factor injections (range: 1-13). No significant ultrasonographic differences were found relative to the incidence of partial or complete posterior vitreous detachment. Vitreous hyperechogenicity increased in the treated eye (P < 0.001), and the vitreous reflectivity range increased with the number of injections (P = 0.041, R = 0.214). However, the type of anti-vascular endothelial growth factor used and the time elapsed since the last intravitreal injection was not significant (P > 0.05). CONCLUSION: These preliminary results indicate a proportional increase in ultrasonographic reflectivity of vitreous gel with the number of injections.

Clinical Decision-Making when Treating Diabetic Macular Edema Patients with Dexamethasone Intravitreal Implants.

Diabetes mellitus (DM) is a metabolic disease frequently associated with comorbidities that include diabetic macular edema (DME). The current medical approach to treating DME involves intravitreal injections with either anti-vascular endothelial growth factors or steroids. However, the burden associated with intravitreal injections and DM-derived complications is high, underlining the need to find optimal treatment regimens. In this article we describe the considerations we apply when treating DME patients with dexamethasone intravitreal implants (Ozurdex®), particularly those that influence the clinical decision-making process during the follow-up period. These considerations are based both on the available medical literature and on our clinical experience following the use of these implants in this type of patient, the goal being to optimize the number of injections and the clinical outcome of this therapy. We also provide a general overview of the pathophysiology of DME, highlighting the inflammatory component as a rationale to use steroids in these patients.

Telemedicine for a General Screening of Retinal Disease Using Nonmydriatic Fundus Cameras in Optometry Centers: Three-Year Results.

PURPOSE: Describe the first 3 years of highly specialized retinal screening through a web platform using a retinologists' network for image reading. METHODS: All patients who came to centers in the network and consented to fundus photography were included. Images were evaluated by ophthalmologists. We describe number of patients, age, visual acuity, retinal abnormalities, medical recommendations, and factors associated with abnormal retinographies. RESULTS: Fifty thousand three hundred eighty-four patients were included; mean age 52.3 years (range 3-99). Mean visual acuity 20/25. Of the total cohort, 75% had normal retinographies, 22% had abnormalities, 1% referred acute floaters, 1% referred acute symptoms with normal retinography, and 1% could not be assessed. Ophthalmological referral was recommended in 12,634 patients: 9% urgent visit, 11% preferential (2-3 weeks), and 80% an ordinary visit. Age-related maculopathy signs were the most common abnormalities (2,456 patients, 4.8%). Epiretinal membrane was the second (764 cases, 1.5%). Diabetic retinopathy was suspected in 543 patients (1%), and nevi in 358 patients (0.7%). Patients older than 50 years had significantly more retinal abnormalities (31.5%) than younger ones (11.1%) (p < 0.0001; odds ratio [OR] 2.47; confidence interval [CI] 2.37-2.57). Patients with almost one eye with a myopic defect greater than -5 spherical equivalent had a higher risk of presenting abnormalities (p < 0.001; OR 1.04; CI 1.03-1.05). CONCLUSIONS: A high rate of asymptomatic retinal abnormalities was detected in this general screening, justifying this practice. Many patients who visit optometrists in Spain are unaware that they would benefit from ophthalmological monitoring. The ophthalmic community should lead initiatives of the type presented to preserve and guarantee quality standards.

Acute loss of vision after an intravitreal injection ocriplasmin: a functional evolutionary study for 1-year follow-up.

INTRODUCTION: Ocriplasmin is a human plasmin fragment indicated for vitreomacular traction treatment. With its increasing use, several reported cases have suggested possible toxicity to the retina. CASE: We describe a case of a 55-year-old woman with symptomatic vitreomacular traction and a macular hole in the right eye who showed an acute decrease in visual acuity after an intravitreal ocriplasmin injection. Spectral-domain optical coherence tomography showed an alteration in the ellipsoid layer. Significant retinal vessel constriction was observed by angiography. The visual acuity improved to 20/100, and the electroretinogram progressively improved after the 1-year follow-up and following pars plana vitrectomy. CONCLUSIONS: A decrease in visual acuity and an enlargement of the macular hole were observed while studying this patient. This study shows the recovery of adverse effects caused by intravitreal injection of ocriplasmin for 1-year follow-up.

Burden of Disease Study of Patients with Neovascular Age-Related Macular Degeneration in Spain.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain. METHODS: The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021. RESULTS: The mean annual cost of nAMD was estimated at €17,265, €15,403, and €14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of €744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year 1; 42% in year 2; 39% in year 3). Similarly, DNHC had an important contribution to the total costs (32% in year 1; 35% in year 2; 37% in year 3), followed by IC (20% in year 1; 23% in year 2; 24% in year 3), while the contribution of patients' LPL was minimal. CONCLUSION: This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression.

Burden of Disease Study of Patients with Diabetic Macular Oedema in Spain.

INTRODUCTION: Diabetic macular oedema (DMO) is a complication of diabetic retinopathy that can result in vision loss. The disease can impact different spheres of a patient's life, including physical and psychological health, work, and activities of daily living, entailing an important use of healthcare and non-healthcare resources. This study aimed to estimate the socio-economic burden of DMO in Spain. METHODS: The burden of DMO was estimated from a societal perspective, per patient, year of treatment since diagnosis, and type of treatment. Four categories were considered: direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labour productivity losses (LPL), and intangible costs (IC) associated with loss of quality of life. Average annual costs were calculated by multiplying the resources used per patient by their corresponding unit price (or financial proxy). For a more accurate estimation, differences in resource use between treatments (intravitreal anti-vascular endothelial growth factor injections of ranibizumab or aflibercept, and intravitreal dexamethasone implants) and year since diagnosis (first, second, and third year or beyond) were considered and presented separately. The reference year for costs was 2021. RESULTS: The average annual costs of DMO in the first year of treatment after diagnosis was estimated at €18,774, €17,512, and €16,188 per patient treated with ranibizumab, aflibercept, and dexamethasone, respectively. This burden would be reduced to €15,783, €15,701, and €12,233 in the second year, and to €15,119, €15,043, and €12,790 in the third year, respectively. Diagnosis of DMO entails an additional one-off cost of €485. DHC accounted for the greatest proportion of total annual costs per patient, independent of the year, with LPL also making an important contribution to total costs. CONCLUSIONS: The socio-economic impact of DMO on patients, the healthcare system, and society at large is substantial. The constant increase in its prevalence accentuates the need for planning and implementation of healthcare strategies to prevent vision loss and reduce the socio-economic burden of the disease.

The Effect of Systemic Parameters and Baseline Characteristics in Short-Term Response Analysis with Intravitreal Ranibizumab in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration.

Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.

Relationships between Patient-Reported Outcome Measures and Clinical Measures in Naïve Neovascular Age-Related Macular Degeneration Patients Treated with Intravitreal Ranibizumab.

Our objective was to evaluate changes in patient-reported outcome measures using the NEI-VFQ 25 questionnaire during a treat and extend regimen in naive neovascular Age-Related Macular Degeneration patients, and its correlation with anatomical and functional data. We conducted a prospective observational study. Patients underwent a treat and extend regimen with intravitreal ranibizumab for neovascular Age-Related Macular Degeneration. Initial response was evaluated at 4th month, and subsequently in every follow-up visit. If a clinical response was achieved, the injection interval was extended in two-week increments, up to a maximum of 12 weeks. Quality of life was assessed using the NEI-VFQ 25 questionnaire at baseline, 4th months, and 12th months. Patients were categorized as good or poor responders based on Best corrected visual acuity, central foveal thickness, intraretinal fluid, or subretinal fluid. Treatment with ranibizumab led to a significant improvement in quality of life, with a mean increase in NEI-VFQ 25 score of 4.27 points in the 12th month. No significant differences in improvement were observed between good and poor responders. Quality of life scores in neovascular Age-Related Macular Degeneration patients improved with intravitreal treatment regardless of the clinical response. The early response following the loading phase could indicate better quality of life after one year of treatment, with Best corrected visual acuity being the clinical parameter with the greatest influence on quality of life.

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.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Influence of Genetic Polymorphisms on the Short-Term Response to Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: To determine whether genetic risk single nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD) influence short-term response to intravitreal ranibizumab treatment. Methods: Forty-four treatment-naive AMD patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD. After an initial clinical examination (baseline measurement), a follow-up visit was performed to determine treatment response one month after the third injection (treatment evaluation). Patients were evaluated based on ophthalmoscopy, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Peripheral venous blood was collected for DNA analysis at baseline visit. Patients were genotyped for single-nucleotide polymorphisms within AMD-relevant genes and classified on good or poor responders based on visual acuity, central retinal thickness, intraretinal fluid, and subretinal fluid. Results: One hundred ten AMD-associated SNPs have been analyzed. Six were found to be relevant when associated to ranibizumab treatment response. The genetic variants rs890293 (CYP2J2), rs11200638 (HTRA1), rs405509 (APOE), rs9513070 (FLT1), and rs8135665 (SLC16A8) predisposed patients to a good response, whereas rs3093077 (CRP) was associated with a poor response. FTL1, SLC16A8, and APOE were the SNPs that showed significance (P < 0.05) but did not pass Bonferroni correction. Conclusions: This is the first study that links novel polymorphisms in genes such as CRP, SCL16A8, or CYP2J2 to treatment response to ranibizumab therapy. On the other hand, HTRA1, FLT1, and APOE are linked to a good ranibizumab response. These SNPs may be good candidates for short-term treatment response biomarkers in AMD patients. However, further studies will be necessary to confirm our findings.

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.

Clinical-Decision Criteria to Identify Recurrent Diabetic Macular Edema Patients Suitable for Fluocinolone Acetonide Implant Therapy (ILUVIEN®) and Follow-Up Considerations/Recommendations.

Current management of diabetic macular edema (DME) predominantly involves treatment with short-acting intravitreal injections of anti-vascular endothelial growth factors (anti-VEGFs) and/or corticosteroids; however, short-acting therapies (lasting between 1 and 6 months) require frequent injections to maintain efficacy, meaning a considerable treatment burden for diabetic patients with multiple comorbidities. Continuous injections needed in some cases are an economic burden for patients/healthcare system, so real-life clinical practice tends to adopt a reactive approach, ie, watch and wait for worsening symptoms, which consequently increases the risk of undertreatment and edema recurrence. On March 7th 2019, a group of experts in retinal medicine and surgery held a roundtable meeting in Madrid, Spain to discuss how to (1) optimize clinical outcomes through earlier use of fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients with persistent or recurrent DME despite therapy; and, (2) to provide guidance to assist physicians in deciding which patients should be treated with ILUVIEN. In this regard, a 36-month follow-up consensus protocol is presented. In conclusion, patients that achieve a complete or partial anatomical, and preferably functional, response following one or two intravitreal dexamethasone implants, but with recurrence of edema after 3-4 months, are deemed by the authors most likely to benefit from ILUVIEN, and the switch to FAc implant should not be delayed more than 12 months after the initiation of at least the first dexamethasone implant.

Pharmacological Advances in the Treatment of Age-related Macular Degeneration.

Age-related macular degeneration is an acquired degenerative disease that is responsible for severe loss of vision in elderly people. There are two types: dry age-related macular degeneration and wet age-related macular degeneration. Its treatment has been improved and tries to be tailored in the future. The aim of this review is to summarize the pharmacological advances in the treatment of age-related macular degeneration. Regarding dry AMD, there is no effective treatment to reduce its progression. However, some molecules such as lampalizumab and eculizumab were under investigation, although they have shown low efficacy. Herein, in an attempt to prevent dry AMD progression, the most important studies suggested increasing the antioxidants intake and quitting the smoke habit. On the other hand, wet AMD has more developed treatment. Nowadays, the gold standard treatment is anti-VEGF injections. However, more effective molecules are currently under investigation. There are different molecules under research for dry AMD and wet AMD. This fact could help us treat our patients with more effective and lasting drugs but more clinical trials and safety studies are required in order to achieve an optimal treatment.

Anti-VEGF Treatment and Response in Age-related Macular Degeneration: Disease's Susceptibility, Pharmacogenetics and Pharmacokinetics.

The current review is focussing different factors that contribute and directly correlate to the onset and progression of Age-related Macular Degeneration (AMD). In particular, the susceptibility to AMD due to genetic and non-genetic factors and the establishment of risk scores, based on the analysis of different genes to measure the risk of developing the disease. A correlation with the actual therapeutic landscape to treat AMD patients from the point of view of pharmacokinetics and pharmacogenetics is also exposed. Treatments commonly used, as well as different regimes of administration, will be especially important in trying to classify individuals as "responders" and "non-responders". Analysis of different genes correlated with drug response and also the emerging field of microRNAs (miRNAs) as possible biomarkers for early AMD detection and response will be also reviewed. This article aims to provide the reader a review of different publications correlated with AMD from the molecular and kinetic point of view as well as its commonly used treatments, major pitfalls and future directions that, to our knowledge, could be interesting to assess and follow in order to develop a personalized medicine model for AMD.