Two Year Study of Aflibercept and Ranibizumab Intravitreal Therapy in Patients with Wet AMD

Background and objectives: The aim of this study was to evaluate the therapeutic results in patients with exudative AMD treated with ranibizumab and aflibercept intravitreal injections over a two-year observation period. Materials and methods: A retrospective observational study was conducted in a clinical hospital on a group of patients who randomly qualified for treatment with Aflibercept (group A) and Ranibizumab (group B) as part of the Polish National Health Fund Medical Program for exudative AMD. Group A consisted of 90 patients, and group B contained 54 patients. The choice of drug in a patient depended solely on the availability of the medication at the time. Before each injection, best corrected visual acuity (BCVA) on the ETDRS scale and central retinal thickness (CRT) were assessed using optical coherence tomography (OCT). Patients from both groups were treated in the first year of treatment with a rigid scheme of 3 doses of 2.0 mg Aflibercept (group A) and 0.5 mg Ranibizumab (group B) at monthly intervals, followed by 4 doses at bimonthly intervals. In the second year, a “pro re nata” scheme was applied. The aim was to evaluate changes in BCVA and CRT after three injections, after 7 injections (about 12 months), and after the second year of therapy (24 months) with reference to the baseline and to compare the effectiveness of the medications. The influences of the following factors were studied: age, gender, initial BCVA, and initial CRT, as well as the number of injections received. Results: No significant statistical differences were found between patients receiving Aflibercept and Ranibizumab therapy in terms of achieving improved visual acuity and reducing retinal thickness after two years of therapy. Conclusions: Both aflibercept and ranibizumab were found to be effective for treating exudative AMD.

ASSOCIATION BETWEEN CENTRAL RETINAL THICKNESS AND VISUAL OUTCOME POST INTRAVITREAL RANIBIZUMAB INJECTION LOADING DOSES IN EXUDATIVE AGE RELATED MACULAR DEGENERATION

Introduction : Age Related Macular Degeneration (AMD) stills the leading cause of blindness in developing countries for age 50 and above, increasing along higher life expectations.Anti- VEGF is the mainstay management for exudative AMD and able to reduce the central retinal thickness (CRT) and to increase the visual outcome. The aim of this study is to correlate between CRT and visual outcome in exudative AMD post intravitreal ranibizumab injection loading doses in Soetomo general academic hospital, Surabaya Methods : This was a retrospective, cross sectional study. Fourty two eyes who met inclusion criterias were received monthly loading doses of 0.5 mg Ranibizumab intravitreal injection for three consequtives months. Baseline visual acuity (BCVA) was measured with Snellen Chart converted to LogMAR, CRT was measured by SD-OCT. Parameters was measured before the first injection and after completed three months injections. Result : Fourty two eyes were composed by 59.5% male and 40.5% female with higher incidence in 61-70 years old (47.6%). Mean BCVA were 0.831 before and 0.624 after injection of serial Ranibizumab. Mean CRT were 346.9 and 254.2 µm before and after injection respectively. There was significant comparison between CRT and BCVA (p=0.00) & no correlation between CRT and BCVA before and after injection of Ranibizumab loading doses (p=0.418 & p=0.275) Conclusion : There were no correlation statistically between CRT and BCVA before and after injection of loading doses Ranibizumab intravitreal in exudative AMD. Further studies may be needed to prove the etiology of this tendencies.

Electrophysiological signs of retinal cone remodeling in geographic atrophy of the pigment epithelium in patients with non-exudative age-related macular degeneration

Testing patients with primary geographic atrophy (GA) requires a multimodal approach and identification of functional biomarkers characterizing retinal structural remodeling.Purpose: to identify the changes in the functional activity of the retinal cone system, which may serve as biomarkers of primary GA in non-exudative age-related macular degeneration (AMD).Material and methods. We tested 22 patients (30 eyes) aged 45–83 (ave. 72.1 ± 10.8 years) with non-exudative AMD and 18 age matched controls (60.2 ± 7.6 years) all of which underwent standard ophthalmological examinations, optical coherence tomography, autofluorescence study, and fundus photography. Standard photopic ERGs, photopic flicker ERGs to stimuli with frequencies of 8.3, 10, 12, and 24 Hz, multifocal ERG (mfERG), and electrooculogram (EOG) were recorded.Results. Electroretinographic signs for GA of retinal pigment epithelium and choriocapillary layer atrophy were described. The results confirm early impairment of the activity of cones in GA and weakening of the functional interaction of M ller cells with the cone bipolar cells. The delayed P1 peak latency of mfERG indicates a decrease in the entire central retina function in non-exudative AMD. A selective reduction in the fovea's mfERG magnitude can serve as a biomarker of primary GA. The spread of the P1 anomaly to adjacent rings may indicate a possible risk of disease progression. A decrease in the dark trough on the EOG and an increase in the Arden ratio can serve as a biomarker of primary GA.Conclusion. We determined electrophysiological signs which can serve as markers of early retinal dysfunction in eyes with primary GA and non-exudative AMD.

Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

The present study aimed to determine the efficacy and safety of pro re nata (PRN) intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) without a loading dose in the real-world setting. The PROBE study (Pro Re Nata Brolucizumab for Exudative AMD) is a retrospective, observational, multicentric study that included 27 treatment-naïve patients (27 eyes) with neovascular AMD who received PRN brolucizumab therapy with the treatment interval being at least 8 weeks, should the need for a second consecutive injection arise. The primary outcome measure was changed to best-corrected visual acuity (BCVA) over time. Secondary outcome measures included the determination of change in central subfield thickness (CST) and complications. The mean follow-up was 11.2 ± 1.2 months. The mean baseline and final BCVA were 57.4 ± 4.5 letters and 65.3 ± 3.12 letters, respectively (p = 0.014). The mean gain in letters at the end of follow-up was 7.8 ± 3.5 letters. There was a significant decrease in CST at the end of the follow-up period (p = 0.013). Patients received a mean of 2.2 ± 0.9 injections (in addition to the first mandatory injection) during the follow-up period. There were no adverse events noted. In conclusion, initial PRN brolucizumab for exudative AMD without a loading dose demonstrated significant visual improvement and no adverse events.

Depression, Anxiety, Somatization Disorder, and Adjustment Disorder in Older Patients with Exudative Age-related Macular Degeneration

Purpose: The aim of this study was to analyze the prevalence of depression, anxiety, somatization disorder, and adjustment disorder in older patients diagnosed with exudative age-related macular degeneration (AMD) and to evaluate the relationship between exudative AMD and psychological disease.Methods: The 2016 Health Insurance Review and Assessment Service-Aged Patient Sample was applied in this study. The subjects were divided into two groups: AMD patients undergoing intravitreal injection treatment and a control group. Comorbidities were evaluated using the Charlson Comorbidity Index.Results: A total of 1,319,052 subjects were selected, of which 3,134 were in the exudative AMD group receiving intravitreal injections. The average age of the subjects was 74.7 ± 6.7 years, and 41.8% were male. In patients with exudative AMD, the prevalence of depression, anxiety, somatization disorder, and adjustment disorder were 16%, 20%, 0.5%, and 0.4%, respectively; in particular, the prevalence of depression and adjustment disorder were significantly higher than in the control group. In multivariate regression analysis, exudative AMD was a significant factor of depression (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.08-1.31, p < 0.001) and adjustment disorder (OR 2.47, 95% CI 1.47-4.18, p < 0.001). However, the association between AMD and anxiety or somatization disorder was not statistically significant.Conclusions: Exudative AMD showed a significant association with psychiatric disease, such as depression, and requires close clinical attention.

Statins and the progression of age-related macular degeneration in the United States

Purpose To study the effect of statin exposure on the progression from non-exudative to exudative age-related macular degeneration (AMD). Methods Retrospective cohort study of commercially insured patients diagnosed with non-exudative AMD (n = 231,888) from 2007 to 2015. Time-to-event analysis of the association between exposure to lipid-lowering medications and time from non-exudative AMD to exudative AMD diagnosis was conducted. Outcome measures included progression to exudative AMD, indicated by diagnosis codes for exudative AMD or procedural codes for intravitreal injections. Results In the year before and after first AMD diagnosis, 11,330 patients were continuously prescribed lipid-lowering medications and 31,627 patients did not take any lipid-lowering medication. Of those taking statins, 21 (1.6%) patients were on very-high-dose lipophilic statins, 644 (47.6%) on high-dose lipophilic statins, and 689 (50.9%) on low-dose lipophilic statins. We found no statistically significant relationship between exposure to low (HR 0.89, 95% CI 0.83 to 1.38) or high-dose lipophilic statins (HR 1.12, 95% CI 0.86 to 1.45) and progression to exudative AMD. No patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD, though this difference was not statistically significant due to the subgroup size (p = .23, log-rank test). Conclusions No statistically significant relationship was found between statin exposure and risk of AMD progression. Interestingly, no patients taking very-high-dose lipophilic statins progressed to exudative AMD, a finding that warrants further exploration.

Intraretinal, sub-retinal, and sub-retinal pigmented epithelium fluid in non-exudative age-related macular degeneration: follow-up with OCT imaging

Background/objectives: To evaluate the presence and evolution of fluid in non-exudative age-related macular degeneration (AMD) through serial OCT. Subjects/methods: A retrospective analysis of eyes with non-exudative AMD with a minimum of 4 year follow-up was done. Parameters including intraretinal fluid (IRF), subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid (SRPEF); subfoveal choroidal thickness (SFCT) and type of drusen were evaluated using optical coherence tomography (OCT) scans at baseline and follow up visits. Results: Seventy-two eyes (in 63 patients) were followed up for an average of 5.83 ± 2.17 years. A total of 26/72 (36%) and 29/65 (52%) of the non-exudative eyes had fluid during baseline and the last visit. Seven eyes (10%) out of 72 eyes converted into exudative AMD or neo-vascular AMD (nAMD) during the study period. SRPEF at baseline was most common fluid location for non-exudative eyes that eventually converted to nAMD. Conclusion: Non-exudative fluid including IRF, SRF, and SRPEF is seen in patients with non-exudative AMD with increasing incidence during long term follow-up.

Progranulin deficiency in Iba-1+ myeloid cells exacerbates choroidal neovascularization by perturbation of lysosomal function and abnormal inflammation

Background Age-related macular degeneration (AMD) is the principal cause of permanent blindness among elderly individuals worldwide. Chronic inflammation in the subretinal space is associated with a progression of exudative AMD. Progranulin (PGRN) is a growth factor secreted from myeloid cells and plays an important role in controlling the lysosomal function. A deficiency in PGRN leads to inflammation of the neurons in the central nervous system. The purpose of this study was to investigate the role played by PGRN in the size of the choroidal neovascularization (CNV) in laser-induced CNV mice. Methods CNVs were induced in C57BL/6J mice by laser photocoagulation of the retina. The expression of PGRN and the accumulation of Iba-1+ cells around the sites of the CNVs were determined. Grn−/−, Grn+/−, and Grn+/+ mice with laser-induced CNVs were also studied. To evaluate the effect of macrophages on the inflammation, we used a macrophage cell line (RAW264.7) in which the expression of PGRN was knocked down by RNA interference and peritoneal macrophages derived from Grn−/− and Grn+/+ mice. These cells were incubated under hypoxic conditions (1% O2). Results Iba-1+ myeloid cells migrated and accumulated in the photocoagulation-induced CNV areas, and the CNV lesions secreted high levels of PGRN in Grn+/+ mice. The size of the CNVs was larger in Grn−/− mice than in Grn+/− and Grn+/+ mice. In Grn−/− mice, the number of ocular-infiltrating Iba-1+ cells around the CNV was higher, and these cells produced more VEGF-A than the cells in the Grn+/+ mice. PGRN-silencing of RAW264.7 cells led to abnormal activation of the cells. In addition, hypoxic conditions promoted the production of proangiogenic and proinflammatory cytokines from PGRN-deficient macrophages. Interestingly, the expression level of lysosome-associated proteins and the number of activated lysosomes increased in PGRN-deficient macrophages. Conclusions These findings indicate that PGRN deficiency in Iba-1+ cells activates the lysosomal function that then leads to abnormal inflammation. The aberrant activation of Iba-1+ myeloid cells might contribute to the progression of the CNV and the regulation of these cells might be a novel therapeutic target for exudative AMD.

The Spectrum of Central Choriocapillaris Abnormalities on Swept-Source Optical Coherence Tomography Angiography in the Fellow Eye of Unilateral Exudative Age-Related Macular Degeneration Patients: From Flow Deficits to Subclinical Non-Exudative Neovascularization

We evaluated the spectrum of choriocapillaris (CC) abnormalities in the fellow eyes of unilateral exudative age-related macular degeneration (AMD) patients using swept-source optical coherence tomography angiography (SS-OCTA). Fellow eyes of unilateral exudative AMD patients were prospectively included between May 2018 and October 2018. Patients underwent a multimodal imaging including a SS-OCTA. Demographics and clinical findings were analyzed. The estimated prevalence of macular neovascularization (MNV) was computed. Number and size of flow deficits (FDs) and percentage of flow deficits (FD%) were computed on the compensated CC flow images with the Fiji software. We included 97 eyes of 97 patients (mean age was 80 ± 7.66 years, 39 males, 58 females). The prevalence of MNV in the studied eyes was 8.25% (8/97 eyes). In the 89 non-neovascular eyes, FD% averaged 45.84% ± 11.63%, with a corresponding total area of FDs of 4.19 ± 1.12 mm2. There was a higher prevalence of drusenoid pigment epithelial detachment in eyes with subclinical neovascularization (p = 0.021). Fellow eyes with unilateral exudative AMD encompassed a series of CC abnormalities, from FDs of the aging CC to subclinical non-exudative MNV.