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.

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.

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.

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.

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.

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.

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.

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.

Intravitreal triamcinolone in diabetic retinopathy.

Diabetic macular edema is an important cause of visual loss in the developed world and may frequently lead to irreversible changes in visual acuity. The Early Treatment Diabetic Retinopathy Study showed a significant benefit in using focal laser photocoagulation for the treatment of macular edema, more specifically defined as clinically significant macular edema. However, some cases of diabetic macular edema are refractory to laser therapy and do not have a good prognosis with such treatment. Triamcinolone acetonide is glucocoticosteroid with antiangiogenic and antiedematous properties. Recently, some promising results, respect to the increases of visual acuity and decreases in foveal thickness, have been shown in different studies for the treatment of refractory diabetic macular edema with intravitreal triamcinolone acetonide.

Confocal microscopy and histopathological examination of diffuse lamellar keratitis in an experimental animal model.

PURPOSE: To investigate the cell populations and structural alterations of the cornea in an experimental model of diffuse lamellar keratitis (DLK) using confocal microscopy and histopathology. METHODS: A corneal flap was cut in 22 eyes of 11 New Zealand rabbits and the stromal interface was exposed to balanced salt solution (BSS, BSS group) and Pseudomonas aeruginosa lipopolysaccharide (LPS) endotoxin (5 mg/mL) (LPS 5 mg/mL group) and (3.5 mg/mL) (LPS 3.5 mg/mL group). Postoperatively, eyes were examined with a slit-lamp microscope (DLK grading) and confocal microscopy. Animals were sacrificed on day 3 (BSS group and LPS 5 mg/mL group) and day 4 (LPS 3.5 mg/mL group). Corneoscleral buttons were excised and processed for histopathologic examination. RESULTS: Seven eyes were excluded. Slit-lamp microscopy revealed no cellular infiltration in the BSS group (five eyes). In the LPS groups, all eyes developed DLK, with iritis only observed in grade III eyes. In the LPS 5 mg/mL group, four eyes had DLK grade III, with iritis in three eyes. In the LPS 3.5 mg/mL group, three eyes had grade II and three eyes had grade III with iritis. On confocal microscopy, the BSS group had no cellular infiltration. Dense accumulation of inflammatory cells at the interface was noted in both LPS groups. Histopathology in the BSS group had a normal appearance. In the LPS groups, an inflammatory infiltrate was present at the interface that consisted of three cell populations--eosinophils, neutrophils, and lymphocytes. CONCLUSIONS: Lipopolysaccharide endotoxin induced DLK in all exposed eyes, with iritis in a considerable proportion of eyes. The infiltrate consisted of three cell populations. Confocal microscopy showed the infiltrate in all affected eyes. Histopathological and confocal microscopic findings correlated well with the clinical appearance.

Successful treatment of retinal angiomatous proliferation by photodynamic therapy.

PURPOSE: The purpose of this study is to describe a patient with retinal angiomatous proliferation (RAP) treated successfully by photodynamic therapy. METHODS: A 74-year-old white woman was referred to our clinic for evaluation as a result of progressive decrease of vision in the right eye. Visual acuity was 20/100 in the affected right eye. The findings of fluorescein and indocyanine green angiography were consistent with a diagnosis of RAP, and cystoid macular edema was also revealed by optical coherence tomography (OCT). Photodynamic therapy (PDT) was carried out because of visual deterioration and localization of the RAP. RESULTS: The RAP was treated with PDT, and an improvement in visual acuity to 20/60 was noted 4 months after treatment and 20/40 after 6 months. The resolution of the lesion was confirmed by fluorescein angiography, indocyanine green angiography, and OCT. CONCLUSIONS: Photodynamic therapy can be effective for the treatment of RAP when it is associated with visual acuity decrease and is located near the fovea.