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Age-related macular degeneration (AMD) is a leading cause of visual impairment. Anti-vascular endothelial growth factor drugs used to treat AMD carry the risk of inducing subretinal fibrosis. We investigated the use of adrenomedullin (AM), a vasoactive peptide, and its receptor activity-modifying protein 2, RAMP2, which regulate vascular homeostasis and suppress fibrosis. The therapeutic potential of the AM-RAMP2 system was evaluated after laser-induced choroidal neovascularization (LI-CNV), a mouse model of AMD. Neovascular formation, subretinal fibrosis, and macrophage invasion were all enhanced in both AM and RAMP2 knockout mice compared with those in wild-type mice. These pathologic changes were suppressed by intravitreal injection of AM. Comprehensive gene expression analysis of the choroid after LI-CNV with or without AM administration revealed that fibrosis-related molecules, including Tgfb, Cxcr4, Ccn2, and Thbs1, were all down-regulated by AM. In retinal pigment epithelial cells, co-administration of transforming growth factor-β and tumor necrosis factor-α induced epithelial-mesenchymal transition, which was also prevented by AM. Finally, transforming growth factor-β and C-X-C chemokine receptor type 4 (CXCR4) inhibitors eliminated the difference in subretinal fibrosis between RAMP2 knockout and wild-type mice. These findings suggest the AM-RAMP2 system suppresses subretinal fibrosis in LI-CNV by suppressing epithelial-mesenchymal transition., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Age-related macular degeneration (AMD) is the leading cause of blindness in older people in the developed world while Stargardt's disease (SD) is a juvenile macular degeneration and an orphan disease. Both diseases are untreatable and are marked by accumulation of lipofuscin advancing to progressive deterioration of the retinal pigment epithelium (RPE) and retina and subsequent vision loss till blindness. We discovered that a small molecule belonging to the tetrahydropyridoether class of compounds, soraprazan renamed remofuscin, is able to remove existing lipofuscin from the RPE. This study investigated the drug penetration, distribution, and elimination into the eyes of a mouse model for increased lipofuscinogenesis, following a single intravitreal injection. We measured the time course of concentrations of remofuscin in different eye tissues using high-performance liquid chromatography combined with mass spectroscopy (HPLC-MS). We also visualized the penetration and distribution of 3 H-remofuscin in eye sections up to 20 weeks post-injection using transmission electron microscopic (TEM) autoradiography. The distribution of silver grains revealed that remofuscin accumulated specifically in the RPE by binding to the RPE pigments (melanin, lipofuscin and melanolipofuscin) and that it was still detected after 20 weeks. Importantly, the melanosomes in choroidal melanocytes only rarely bind remofuscin emphasizing its potential to serve as an active ingredient in the RPE for the treatment of SD and dry AMD. In addition, our study highlights the importance of electron microscopic autoradiography as it is the only method able to show drug binding with a high intracellular resolution., (© 2020 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Purpose: Patients with neovascular age-related macular degeneration (nARMD) will not deteriorate on visual acuity and retinal thickness when treated with bevacizumab injection frequencies of 6 or 8 weeks compared to 4 weeks. This study aimed to investigate this non-inferiority in quality of life (QoL). We hypothesized that less frequent bevacizumab injections are not inferior regarding patients reported QoL., Methods: Patients were randomized to bevacizumab every 4 (n = 64), 6 (n = 63), and 8 weeks (n = 64). Patients were at least 65 years old, have a best-corrected visual acuity of 20/200 to 20/20, no previous ARMD treatment and active leakage. Vision-related QoL questionnaire NEI VFQ-39 was used to assess QoL at baseline and after 1 year. General QoL questionnaire SF-36 was included for secondary analysis. Multilevel analyses were performed, correcting for age, gender and baseline., Results: The 6 (3.68; 95% CI - 0.63 to 8.00) and 8 (2.15; 95% CI - 2.26 to 6.56) weeks bevacizumab regimens resulted in non-inferior QoL differences compared to 4 weeks on the NEI VFQ-39. Also on the SF-36 the differences were well within the non-inferiority limits., Conclusion: Non-inferiority of the 6 and 8 weeks frequencies was demonstrated compared to 4 weeks on vision-related and general QoL in patients with nARMD. These results are in line with previously published results of lower frequency injections regarding visual acuity and central retinal thickness. Lower injection frequency may reduce burden, side effects, and treatment costs. In consideration of these results, 8 weeks frequency injections of intravitreal bevacizumab could be considered in patients with nARMD.

Purpose: To evaluate the periodicity of the intervals of lesion reactivation in patients with neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 139 eyes diagnosed with treatment-naive neovascular AMD and treated with antivascular endothelial growth factor (VEGF) therapy. Patients were initially treated with 3 loading anti-VEGF injections using either ranibizumab or aflibercept. Additional treatment was administered only when lesion reactivation was noted. The difference between the time intervals to the first and the second reactivations was evaluated. The included eyes were divided into 2 groups according to the time interval to the first reactivation: the early reactivation group (≤6 months, n  = 86) and the late reactivation group (>6 months, n  = 53). The association between the time intervals to the first and the second reactivations was evaluated within each group. Results: The mean follow-up period was 52.7 ± 8.9 months. The first reactivation was noted at mean 9.4 ± 10.4 months after the loading injections. The second reactivation was noted at mean 6.2 ± 4.9 months after the treatment for the first reactivation. The time interval to the second reactivation was significantly shorter compared with the first reactivation ( P  = 0.018). The association between the time interval to the first and the second reactivations was significant only in the early reactivation group ( P  = 0.002). Conclusions: A short first reactivation interval suggests that there is a high likelihood that the second reactivation will also be short. However, a long first reactivation interval does not suggest that the second reactivation interval will be similarly long.

Background: Age-related macular degeneration (AMD) is the third largest cause of blindness worldwide, accounting for 8.7% of all cases. A considerable number of preventive or therapeutic interventions have been used for AMD., Objective: This study presents a critical view of the interventions that have been assessed through Cochrane systematic reviews., Design and Setting: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP)., Methods: Review of Cochrane systematic reviews about interventions for AMD., Results: The 18 systematic reviews included assessed the effects of surgical techniques, laser/photo/radiotherapy, intravitreal injections, systemic drugs and phytotherapy/vitamins/supplements., Conclusion: The Cochrane systematic reviews found evidence that use of bevacizumab, ranibizumab, pegaptanib, laser photocoagulation, photodynamic therapy and multivitamin compounds may present some benefits for treating AMD. There was insufficient evidence for supporting the use of macular translocation, submacular surgery, steroid implantation, radiotherapy, intravitreal aflibercept, interferon alfa, statins or omega-3 fatty acids for treating AMD; or the use of multivitamin antioxidant vitamins or mineral supplementation for preventing AMD. Future randomized controlled trials are imperative to reduce the uncertainty in several clinical questions regarding AMD.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy.

Purpose: To evaluate safety and efficacy of the vascular endothelial growth factor binding protein abicipar pegol (abicipar) versus ranibizumab for neovascular age-related macular degeneration. Methods: Phase 2, multicenter, randomized, double-masked comparison (REACH study, stage 3). Patients ( n  = 64) received intravitreal injections of abicipar 1 mg or 2 mg at baseline, week 4, and week 8 (3 injections) or ranibizumab 0.5 mg at baseline and monthly (5 injections). Results: In the abicipar 1 mg ( n  = 25), abicipar 2 mg ( n  = 23), and ranibizumab ( n  = 16) arms, respectively, least-squares mean best-corrected visual acuity (BCVA) change from baseline was +6.2, +8.3, and +5.6 letters at week 16 (primary endpoint) and +8.2, +10.0, and +5.3 letters at week 20. Least-squares mean central retinal thickness (CRT) reduction from baseline was 134, 113, and 131 μm at week 16 and 116, 103, and 138 μm at week 20. Intraocular inflammation adverse events (AEs), reported in 5/48 (10.4%) abicipar-treated patients, resolved without sustained vision loss or other sequelae. Conclusions: Abicipar demonstrated durability of effect: BCVA and CRT improvements were similar between abicipar and ranibizumab at weeks 16 and 20 (8 and 12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection). No serious AEs were reported.

Purpose: To describe a technique for extemporaneously drawing up bevacizumab for intravitreal injection (IVT) and report the rate of post-injection endophthtalmitis., Patients and Methods: Retrospective monocentric analysis (January 2010-December 2014) of all IVT of bevacizumab drawn up with the following technique: in the operating room (class ISO 7) through a mini-spike with an integrated bacteria retentive air filter. The surgeon was wearing sterile gloves and a mask. The assisting nurse wore a mask. The bevacizumab vial was discarded at the end of each session., Results: Six thousand two hundred and thirty-six bevacizumab injections were performed. One case of endophthalmitis was noted (0.016%). During the same period, 4 cases of endophthalmitis were found after IVT of other drugs (4/32,992; 0.012%. P=0.8)., Conclusion: Intravitreal injection of bevacizumab after extemporaneous withdrawal through a mini-spike filter is a simple and safe technique. The risk of postoperative endophthalmitis is very low. This simple technique facilitates access to compounded bevacizumab., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: To assess UK practice patterns related to the prescription of antibiotics before, during and after intravitreal injections, the location where injections are carried out and the qualifications of those administering the injections., Methods: Every ophthalmology unit featured in the Royal College of Ophthalmologists (UK) training directory was contacted. A healthcare professional involved in giving intravitreal injections at each institution completed a questionnaire regarding local practice patterns., Results: A response rate of 85% (115/136) was achieved. Seventy four percent of hospitals (85/115) gave take home antibiotics post intravitreal injection. Twenty three percent (26/115) of hospitals employed non-medical healthcare professionals to administer injections and 83% (96/115) administered intravitreal injections in a dedicated clean room as opposed to an operating theatre., Conclusion: Practice patterns for intravitreal injection vary considerably. Guidelines alone do not appear to be effective in reducing practices which are considered wasteful and other approaches need to be developed., (© 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.)

Purpose: To report the anatomical and visual results in patients diagnosed as having retinal pigment epithelium (RPE) tears after receiving ranibizumab injections., Methods: Eyes diagnosed as having RPE tears with a minimum 6-month follow-up were retrospectively evaluated. Each eye was treated with at least three doses of ranibizumab at monthly intervals. Best-corrected visual acuity (BCVA), anterior segment findings, intraocular pressure, and fundus examination results were evaluated during control visits. Color fundus photography, fundus fluorescein angiographies, fundus autofluorescence, and spectral domain optical coherence tomography (SD-OCT) images were obtained. The height of pigment epithelial detachment (PED) was measured by SD-OCT., Results: Twelve eyes with RPE tears were studied. Nine eyes (75%) developed RPE tears during ranibizumab injections for choroidal neovascularization (eight eyes with vascularized PED and one eye with choroidal osteoma), and tears occurred in three eyes before any injections. The median number of ranibizumab injections after diagnosis of RPE tears was 3 (min 2, max 5). In the most recent follow-up visit, there was no statistically significant correlation between the grade of RPE and logMAR of BCVA (p>0.05, r=0.112). Eight of twelve eyes had PED, and seven of these had irregular PED contours before injection therapy. The mean PED height was 447 ± 122 µm., Conclusions: In this series, RPE tears developed mostly after intravitreal anti-VEGF injections for vascularized PED. Increased vertical height and irregular contours of the PEDs can be risk factors for the formation of RPE tears. The continuation of anti-VEGF therapy after tear formation is beneficial for vision improvement in eyes with RPE tears.

Purpose: To determine the intravitreal anti-vascular endothelial growth factor (VEGF) injection techniques and preferences within the retinal community and to identify potential factors associated with the development of sustained intraocular pressure (IOP) elevation in patients treated with intravitreal anti-VEGF therapy for neovascular age-related macular degeneration (AMD)., Design: Cross-sectional physician survey., Methods: Five hundred and thirty retina specialists spanning both private and academic practices were surveyed regarding current anti-VEGF intravitreal injection protocols, including the anti-VEGF drug of choice, needle gauge, injection volume, injection technique, and self-reported prevalence of sustained IOP elevation. Multivariate logistic regressions were performed to assess the potential influence of these factors on long-term IOP., Results: Two hundred ninety-two specialists (55%) reported believing that intravitreal anti-VEGF therapy may cause sustained IOP elevation. Of these responses, the most common reported prevalence was 1%-2% (48%), followed by 3%-5% (34%). There was no relationship between the frequency of sustained IOP elevation and anti-VEGF drug of choice. Physicians who injected greater than 0.05 cc in less than 1 second were 5.56 times more likely to observe a high frequency of sustained IOP elevation (P=.006, 95% CI 1.64-18.89)., Conclusions: Based on physician survey data, serial anti-VEGF injections using higher injection volumes with a rapid injection technique may potentially lead to sustained IOP elevation. The underlying mechanism for this complication may be injury to the trabecular meshwork resulting from rapid elevations in IOP. Further investigation of the relationship between injection techniques and sustained IOP elevation in the form of retrospective or prospective clinical studies is warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To describe retinal changes during Spectral Domain Optical Coherence Tomography (SD-OCT) guided bevacizumab treatment for neovascular age- related macular degeneration (AMD)., Settings and Design: Single center observational study., Materials and Methods: We confirmed wet AMD in 47 eyes of 45 patients by fluorescein angiography and SD-OCT. After bevacizumab injection, we examined the patients at 4-week intervals. During each follow-up control, we performed SD-OCT and a complete ophthalmic examination. Criteria for reinjection were visual acuity loss of more than five ETDRS letters, and/or increase of central retinal thickness, sub-retinal fluid, intra-retinal fluid, pigment epithelium detachment. If reinjection criteria were not met, we advised the patient to return in 4 weeks' time for the next scheduled follow-up. We used 3-dimensional SD-OCT to measure photoreceptor defects and sub-retinal fibrosis. The main efficacy endpoints were the SD-OCT measurements of the size of photoreceptor defects, the size of external membrane defects and the central retinal thickness., Results: Over the 12 months study period, the percentage of scans in 3-D imaging mode showing visible defects of the junction between inner and outer segments of photoreceptors increased from 38.96 to 53.8%. The percentage of scans in 3-D imaging mode with visible sub-retinal fibrosis increased from 33 to 52% and mean central retinal thickness decreased from 333 μm (96-900 μm) to 272 μm (P = 0.011)., Conclusion: In long-term anti- Vascular endothelial growth factor (VEGF) treatment for neovascular AMD, photoreceptor defects and fibrosis progress despite a decrease in central retinal thickness and improvements in visual acuity. We would encourage further discussion as to whether this is the natural course of the disease or a result of the treatment.

Purpose: To study the visual outcomes and change in central macular thickness (CMT) in patients with neovascular age-related macular degeneration (AMD) who were previously treated with ranibizumab (Lucentis) and/or bevacizumab (Avastin) and were subsequently switched to aflibercept (VEGF Trap-Eye; Eylea)., Methods: Retrospective study of patients who received intravitreal aflibercept from December 2011 to December 2012 and had previous anti-vascular endothelial growth factor treatment for AMD. The main outcome measures were best-corrected visual acuity (BCVA) and CMT as measured by optical coherence tomography., Results: The study population included 30 patients aged 80.4±1.45 (mean±SEM) who received 6.27±0.37 (range 4-11) aflibercept injections. Eighteen patients had previously received only bevacizumab (12.4±2.18 injections), 2 had received only ranibizumab (19±6 injections), and 10 had received both ranibizumab and bevacizumab (mean 19.3 injections). BCVA logMAR at the initial visit (aflibercept initiation) was 0.506±0.054 (mean VA 20/64), and then, follow ups at 1-month 0.504±0.055 (20/64) P=0.903, 3-months 0.458±0.061 (20/57) P=0.112, 6-months 0.413±0.071 (20/52) P=0.036, and 12-months 0.521±0.076 (20/66) P=0.836. CMT at the initial visit was 261±10.9, and then, at 1-month 238±12.4 P=0.021, 3-months 245±10.6 P=0.102, 6-months 245±10.4 P=0.099, and 12-months 237±10.2 P=0.012. Results were similar in a subset of patients (n=15) with central macular edema or submacular fluid at aflibercept initiation. While on aflibercept, 2 patients developed intraocular pressure increases that required treatment., Conclusions: These findings demonstrate a significant decrease in CMT but no statistically significant improvement in BCVA through the 12-month follow up in patients previously treated who were switched to aflibercept for AMD. Patients may develop ocular hypertension after multiple aflibercept injections.

Aim: This study was conducted to evaluate the possible clinical and genetic indicators for an early response to intravitreal ranibizumab (IVR) in exudative age-related macular degeneration (AMD)., Patients & Methods: The records of 120 eyes from 120 Japanese patients with treatment-naive exudative AMD were retrospectively reviewed. Three consecutive IVR treatments were performed every month. Achievement of anatomical resolution was evaluated by ophthalmoscopy and optical coherence tomography. Multivariable logistic regression analysis was conducted by analyzing SNPs in the ARMS2 locus (A69S) and in the CFH gene (I62V and Y402H), in addition to clinical factors., Results: The mean central retinal thickness of overall patients was significantly decreased (-120.1 ± 122.8 µm, p = 2.7 × 10(-19)) at 3 months after the initial treatment. In the logistic regression analysis, the poor anatomical resolution of the lesion at 3 months was associated with the combination of CFH I62V + CFH Y402H variants (p = 0.0021), and the polypoidal choroidal vasculopathy lesions (p = 0.044)., Conclusion: The CFH variants and the polypoidal choroidal vasculopathy lesion may influence the early anatomical resolution with IVR in exudative AMD.

Introduction: Wet or exudative age-related macular degeneration (AMD) is the leading cause of blindness in the United States for individuals over the age of 65 years. Wet AMD is characterized by the formation of choroidal neovascularization, which can lead to edema, hemorrhage and scarring of the macula. This leads to metamorphopsia and vision loss. Without treatment, the loss of vision is permanent. The current gold standard treatment of wet AMD consists of intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications., Areas Covered: Numerous new therapies in the drug pipeline aim at addressing limitations of current treatments. Future therapies involve novel compounds that attack different parts of the VEGF cascade, novel delivery systems aimed at reducing the frequency of intraocular injections, combination therapies and the use of radiation in conjunction with intravitreal therapies., Expert Opinion: Limitations of current treatments include the need for repeated injections, the high financial costs and treatment burdens of repeated injections, the risk of adverse ocular and systemic adverse events, and the inability to completely reverse the disease process of wet AMD. There are many new therapies and approaches in the pipeline which hold promise for improving the treatment of wet AMD.

Purpose: To describe 1-year clinical results of intravitreal ranibizumab treatment in patients with choroidal neovascularization secondary to exudative age-related macular degeneration (AMD) and to evaluate whether early treatment is a predictive value for prognosis of the disease., Materials and Methods: Clinical records were retrospectively reviewed of 104 eyes that underwent intravitreal ranibizumab therapy for exudative AMD. Patients were divided into two groups according to their symptom duration: group 1, <1 month; and group 2, 1-3 months. After three monthly injections, patients were examined monthly, and subsequent injections were performed as needed., Results: There were 43 female (48.9%) and 45 males (51.1%). The follow-up time was 13.7±1.9 (12-19) months. The mean logarithm of minimum angle of resolution best-corrected visual acuity (BCVA) improved significantly, from 0.45±0.639 at baseline to 0.08±0.267 at 12 months in group 1, and from 1.06±0.687 at baseline to 0.75±0.563 at 12 months in group 2. The increase in BCVA was statistically significant in group 1 (P=0.009). The mean central retinal thickness (CRT) decreased significantly, from 355.13±119.93 μm at baseline to 250.85±45.48 μm at 12 months in group 1, and from 371.88±91.047 μm at baseline to 268.61±53.51 μm at 12 months in group 2. The decrease in CRT was statistically significant in group 1 (P=0.001)., Conclusion: Intravitreal ranibizumab therapy was effective in significantly increasing mean BVCA and reducing CRT. Shorter duration of AMD, as measured by the subjective duration of visual symptoms, is associated with better visual outcome after treatment.

Background: The number of patients treated with intravitreal injections has increased significantly over the past few years, mainly following the introduction of anti-vascular endothelial growth factor antibody intraocular drugs. Bevacizumab is mostly used in this group of medications., Objectives: To describe persistent elevation of intraocular pressure (IOP) following intravitreal injection of bevacizumab., Methods: We reviewed consecutive cases of persistent IOP elevation after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). A total of 424 patients (528 eyes) met the inclusion criteria and received 1796 intravitreal injections of bevacizumab. Persistent IOP elevation was found in 19 eyes (3.6%, 19/528) of 18 patients (4.2%, 18/424) with IOP elevated 30-70 mmHg 3-30 days after injection., Results: Mean IOP was 42.6 mmHg (range 30-70); IOP elevations occurred after an average of 7.8 injections of bevacizumab (range 3-13). Injected eyes (19/528) had a significantly higher incidence of elevated IOP than uninjected eyes (fellow eyes), 1/328, P < 0.001., Conclusions: Like other anti-vascular endothelial growth factor (VEGF) substances reported in a few recent studies, intravitreal injection of bevacizumab for neovascular AMD may be associated with persistent IOP elevation. Providers should be aware that significant IOP elevation might occur after repeated treatments.

Aim: To investigate the association between VEGF gene SNPs and early response to intravitreal ranibizumab for exudative age-related macular degeneration., Materials & Methods: Sixty-four patients (64 eyes) were prospectively enrolled and treated for neovascular age-related macular degeneration with ranibizumab monotherapy. Visual acuity was measured using the ETDRS chart. A loading phase of 3 monthly intravitreal injections of ranibizumab 0.5 mg/0.05 ml was performed. The analyzed VEGF-A gene SNPs were rs699947 (-2578A/C) and rs1570360 (-1154G/A); the allelic discrimination was performed in real-time PCR platform. The difference of best corrected visual acuity (ETDRS letters) read before and after treatment was considered as functional outcome., Results: Ranibizumab was significantly more effective as measured by best corrected visual acuity in patients harboring the VEGF-A -2578C allele (from +6.26 to +7.44 ETDRS letters), whereas patients carrying the VEGF-A -2578AA genotype revealed an absence of early functional response to ranibizumab (-1.78 ETDRS letters; p = 0.0192)., Conclusion: This study suggests that the VEGF-A -2578A/C SNP may represent an important molecular determinant of the early functional outcome of ranibizumab. Original submitted 3 December 2012; Revision submitted 18 February 2013.

Purpose: To assess serum level changes of antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD), treated with transpupillary thermotherapy (TTT) alone and with TTT combined with injection of triamcinolone acetonide (sTTA) under posterior Tenon's capsule and to compare the efficacy of TTT and TTT+sTTA. The purpose of the study was also to estimate if serum ARA may act as the biomarker of AMD., Material and Methods: This prospective study comprised 46 patients (46 eyes) with exudative AMD. Patients were assigned into: group I (n = 24) received TTT alone and group II (n = 20) received TTT with sTTA. Follow-up was at 3, 6, 9 and 12 months, when best-corrected visual acuity (BCVA), Amsler grid-test, intraocular pressure (IOP), fluorescein angiography (FA) and central retinal thickness (CRT) by optical coherence tomography (OCT) were assessed. In all patients serum ARA was determined using indirect immunofluorescence (IIF) method on normal monkey retina as antigens substrate and FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody., Results: Baseline serum ARA titres in group I ranged from 1: 40 to 1: 5120 and in group II--1: 40 to 1: 1280 (p = 0.1). In control group serum ARA was present in 46.4% of sera in titres from 1: 10 to 1: 40. These differences were statistcally significant (p < 0.001). Nine fluorescence patterns of ARA were detected by IIF method in both groups of AMD patients, while control sera showed only three types of reaction. Statistically significant correlation was found between CNV size, CRT and serum ARA titres in both groups of patients (p < 0.01). In a follow-up period decreasing serum ARA titres were noted, specially for subjects treated with combined therapy, however it was not statistically significant at 3, 6 and 9 months while achieved significance (p < 0.01) at month 12. BCVA improvement or stabilization was observed in 64% of eyes in group I and in 75%--in group II (p = 0.1). No leakage on FA was found in 66.7% and 70% of cases, in group I and II, respectively (p = 0.01). CRT reduction was observed in 50% (group I) and in 70% (group II) of eyes (p = 0.01) at month 12., Conclusions: Our preliminary observations indicate that serum ARA changes may reflect the activity of CNV in a course of AMD and may act as the biomarker of treatment efficacy. The use of sTTA in conjunction with TTT for CNV in AMD showed a tendency towards lower serum ARA titres and better functional results after treatment as compared with eyes treated with TTT alone.

Unlabelled: Endophthalmitis is one of the most dangerous complications after intravitreous drug injection. Preparing a patient to the injection general and topical endophtalmitis development risk factors should be eliminated. Antibiotic injection prophylaxis is still an important issue., Purpose: This research has to evaluate effectiveness and tolerance of Azithromycin (Azyter, Thea), in injection as an antibiotic prophylaxis in patients suffering from age-related macular degeneration (AMD)., Material and Methods: The study was conducted in Ophtalmology Department (Medical Military Institute, Warsaw, Poland), in the group of 52 patients, who underwent 52 intraocular injections of anti-VEGF because of AMD. Topical Azithromycin had been administrated twice a day to both eyes in 2 days before injection. On the third day injection was performed in aseptic conditions. One drop of Azithromycin had been administrated to each eye directly before injection and one drop after the procedure. At that moment antibiotic prophylaxis was terminated., Results: Topical tolerance and effectiveness were evaluated. In 2 cases (3.8%) intensive allergic reaction was reported (significant conjuctives oedema, itch, bloodshot), what caused change of antibiotic. In 5 cases (9%) light bloodshot was reported. 12 patients (23%) reported light or moderate foreign body sensation and in 2 cases (3.8%) the sensation was significant. No reaction of ophthalmic inflammation was reported 5 days after injection, moreover foreign body sensation and bloodshot were absent. 30 patients (57%) were satisfied with new and simplier scheme of antibiotic injection prophylaxis (twice a day for 3 days)., Conclusions: Azithromycin is a comfortable alternative for other topical antibiotics, especially in repetitive procedures like anti-VEGF injections. High Azithromycin concentration in tissues, tear film, and on the ophthalmic surface, protects injection site and inhibits growth of primary and mutual bacterial colonies. Short-term exposition to Azithromycin decrases risk of drug resistance development.

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmacokinetics do vary between individuals with AMD, developing a personalized strategy could improve safety and efficacy. This has to be derived from clinical measurements and data from laboratory animals; however, it is recognized that the animal models used in the development of intraocular formulations differ in their vitreous geometry from humans. These factors may be of relevance to the design of ophthalmic formulations and optimizing treatment outcomes in AMD. Further studies are needed to drive improvements in clinical practice which are aimed at maximizing the efficacy profile in IVT for AMD by a more rigorous evaluation of patient and surgeon-related variables., (Copyright © 2010 Elsevier Ltd. All rights reserved.)