Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study).

PURPOSE:: To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. METHODS:: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. RESULTS:: In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. CONCLUSION:: Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.

OM-101 Decreases the Fibrotic Response Associated with Proliferative Vitreoretinopathy.

PURPOSE: This study aimed to investigate the effect of OM-101 on the fibrotic response occurring in proliferative vitreoretinopathy (PVR) in an animal model. METHODS: Antifibrotic effect of OM-101 was investigated in vivo. As control, eight weeks old c57black mice underwent intravitreal injection with Hepes (group A) or dispase (0.3 units), to induce retinal detachment (RD) and PVR. The dispase-injected mice were randomly divided into two groups B and C (N = 25 mice); in group C, the eyes were treated with intravitreal injection of OM-101 (3 µl), and group B with PBS, as a control. After additional five days, mice were injected with the same initial treatment. Three days later, mice were euthanized, and the eyes were enucleated and processed for histological analysis. RESULTS: Intravitreal injection of dispase caused RD in 64% of the mice in group B, and 93% of those mice had PVR. Only 32% of mice treated with OM-101 and dispase (group C) developed RD, and only 25% of those developed PVR. CONCLUSIONS: OM-101 was found effective in reducing the incidence of RD and PVR maintaining the normal architecture of the retina. This study suggests that OM-101 is a potentially effective and safe drug for the treatment of PVR patients.

Efficacy of nepafenac ophthalmic suspension 0.1% in improving clinical outcomes following cataract surgery in patients with diabetes: an analysis of two randomized studies.

OBJECTIVE: To assess the efficacy of nepafenac 0.1% ophthalmic suspension in improving the clinical outcomes following cataract surgery (CS) in patients with nonproliferative diabetic retinopathy. METHODS: In two similar multicenter, randomized studies, patients received either nepafenac 0.1% or vehicle, instilled three times daily starting a day prior to surgery and continuing for 90 days postoperatively. A post hoc analysis of these two studies was conducted to assess 1) the likelihood for development of postoperative macular edema (ME), based on the percentage of patients who developed ME (≥30% increase from preoperative baseline in central subfield macular thickness) within 90 days following CS and 2) best-corrected visual acuity (BCVA) endpoints, including the percentage of patients with a BCVA improvement of ≥15 letters from preoperative baseline to Day 14 and maintained through Day 90. Results for individual studies and their pooled estimates (only visual acuity endpoints) are reported. Primary inference was based on odds ratio (OR). RESULTS: This post hoc analysis included 411 patients (nepafenac 0.1%: 205; vehicle: 206). The incidence of postoperative ME within 90 days of CS was notably lower in the nepafenac-treated patients than in vehicle-treated patients (study 1: 3.2% vs 16.7%; OR =0.2, 95% confidence interval [CI] =0.1, 0.5, P=0.001; study 2: 5.0% vs 17.5%; OR =0.2, 95% CI =0.1, 0.8, P=0.018). A higher percentage of nepafenac-treated patients than vehicle-treated patients gained ≥15 letters from preoperative baseline to Day 14, which was maintained through Day 90 (study 1: 38.4% vs 21.4%; OR =2.4, 95% CI =1.4, 4.2, P=0.003; study 2: 35.0% vs 25.0%; OR =1.6, 95% CI =0.8, 3.2, P=0.172; pooled: 37.1% vs 22.8%; OR =2.0, 95% CI =1.3, 3.1, P=0.001). The odds of >5-letter and >10-letter loss in BCVA from postoperative Day 7 were higher in vehicle-treated than in nepafenac-treated patients. CONCLUSION: These results support the clinical benefit of prophylactic use of nepafenac 0.1% for reducing the risk of postoperative ME and for improvement in BCVA outcomes following CS in patients with nonproliferative diabetic retinopathy.

[PHACOEMULSIFICATION IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION (AMD)].

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. The debate continues over the safety of cataract surgery in the setting of neovascular (wet) AMD. This retrospective review aims to describe our experience in treating patients with wet AMD, who underwent cataract surgery by phacoemulsification. METHODS: We prepared a retrospective chart review of patients treated in our clinic between the years 2006 - 2013. RESULTS: Forty-two eyes of 38 patients were included. Visual acuity (VA) improved significantly 1 month after cataract removal, without a significant change in retinal thickness. Twenty-six patients (62%) needed anti-VEGF injections during follow-up after surgery within an average period of 6 months. In eyes that were dry preoperatively, the re-injection rate was lower than those that were still wet (56 % vs. 80%) and the time from surgery to the first injection was longer in dry eyes (7 months and 3 months, respectively). Eyes that were injected with anti-VEGF up to one week before surgery had greater improvement in VA immediately after surgery but the proportion of those receiving injections (78%) was greater and the time to first injection post-surgery was earlier (3 months) compared to eyes that received the last injection 6 months or more prior to surgery ( 53 % and - 7 months). CONCLUSIONS: Cataract removal improves vision in wet AMD patients. It is of great importance to treat these patients and try to reach dry retina prior to surgery and a close followup is needed after surgery. In eyes that were more stable within 6 months before surgery and their retina was dry, the re-injection rate post surgery was lower and the time to first injection was longer.

[TREATMENT OPTIONS FOR DIABETIC MACULAR EDEMA].

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of vision loss in people under 65 years of age. Diabetic macular edema (DME) is the most common cause of moderate visual impairment in individuals with DR. Until recently, focal or grid laser photocoagulation has been the standard of care for DME. Laser photocoagulation has been shown to stabilize vision and prevent moderate vision loss. Recent studies on the effect of anti-vascular endothelial growth factor (VEGF) substances in DME, showed resolution of the edema and visual acuity gain. Thus, anti-VEGF therapy has become the first line of treatment for DME. Intravitreal steroids, also play a role in the management of DME, particularly in refractory cases, due to their antiinflammatory effect. This review focuses on the emerging treatment options in the management of DME.

Nepafenac 0.3% after Cataract Surgery in Patients with Diabetic Retinopathy: Results of 2 Randomized Phase 3 Studies.

PURPOSE: To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes. DESIGN: Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies. PARTICIPANTS: Total, 615 patients in study 1 and 605 patients in study 2. METHODS: Patients were randomized (1:1) to topical nepafenac 0.3% or vehicle once-daily starting the day before surgery and continuing for 90 days thereafter. MAIN OUTCOME MEASURES: Key efficacy variables were: patients (%) in whom macular edema (ME) developed (≥30% increase from preoperative baseline central subfield macular thickness) within 90 days after cataract surgery and the patients (%) with a best-corrected visual acuity (BCVA) improvement of ≥15 letters from preoperative baseline through day 14 maintained through day 90. Secondary end points included: patients (%) with a BCVA improvement of ≥15 letters from preoperative baseline through days 90 and 60 and safety over 3 months. RESULTS: A significantly lower percentage of patients demonstrated ME within 90 days after surgery with nepafenac 0.3% versus vehicle (study 1: 2.3% vs. 17.3%; P < 0.001; study 2: 5.9% vs. 14.3%; P = 0.001; pooled: 4.1% vs. 15.9%; P < 0.001). The percentage of patients achieving a ≥15-letter improvement from baseline through day 14 maintained through day 90 with nepafenac 0.3% versus vehicle was 61.7% versus 43.0% (P < 0.001) in study 1, 48.8% versus 50.5% (P = 0.671) in study 2, and 55.4% versus 46.7% (P = 0.003) in the pooled analysis. A greater percentage of patients treated with nepafenac 0.3% versus vehicle in study 1 and similar percentage in study 2 had a BCVA improvement of ≥15 letters from preoperative baseline through day 90 (77.2% vs. 67.7% [P = 0.009] and 65.4% vs. 65.9% [P = 0.888]) and through day 60 (76.2% vs. 64.7% [P = 0.002] and 68.9% vs. 62.1% [P = 0.092]). No unanticipated adverse events were observed. CONCLUSIONS: These studies demonstrated the clinical benefits of nepafenac 0.3% over vehicle in reducing the risk of postoperative ME, with the integrated analysis showing improved BCVA after cataract surgery in patients with diabetic retinopathy, with no unanticipated safety events.

Prospective randomised clinical trial to evaluate the safety and efficacy of nepafenac 0.1% treatment for the prevention of macular oedema associated with cataract surgery in patients with diabetic retinopathy.

BACKGROUND/AIMS: This study evaluated nepafenac ophthalmic suspension 0.1% for prevention of macular oedema (MO) when used 90 days following cataract surgery in patients with diabetic retinopathy (DR). METHODS: Randomised, double-masked, vehicle-controlled, parallel group study conducted at 32 centres across the world. Participants were patients with diabetes with non-proliferative diabetic retinopathy scheduled for cataract surgery with (posterior chamber) intraocular lens implantation. Patients were randomised to nepafenac ophthalmic suspension 0.1% or vehicle three times daily, beginning on the day before surgery and continuing through the last study visit (day 90 or early exit). All patients were instilled one drop of tobramycin 0.3% and dexamethasone 0.1% four times daily for 2 weeks after surgery. Primary efficacy end point was the percentage of patients who developed MO (defined as ≥30% increase in central subfield macular thickness from baseline) within 90 days following surgery. The secondary end point was mean change in best-corrected visual acuity (BCVA) from baseline to day 90. RESULTS: A total of 175 patients were randomised, with 87 and 88 patients in the nepafenac and vehicle groups, respectively. A significantly greater percentage of eyes in the vehicle group (17.5%; 95% CI 9.9% to 27.6%) developed MO within 90 days following surgery compared with the nepafenac group (5.0%; 95% CI 1.4% to 12.3%, p=0.01). Mean change in BCVA from baseline to day 90 following surgery was greater in the nepafenac group (17.7±14.6 letters) relative to the vehicle group (14.3±13.9 letters), though the difference was not statistically significant (p=0.14). No new safety issues or trends were identified. CONCLUSIONS: A 90-day nepafenac treatment regimen prevented MO after cataract surgery in patients with DR and demonstrated no safety issues within this study group. TRIAL REGISTRATION NUMBER: NTC00782717 and NCT00939276.

TAK1 is involved in the autophagy process in retinal pigment epithelial cells.

Autophagy is an evolutionarily conserved mechanism for degrading long-lived or malfunctioning proteins and organelles, such as those resulting from oxidative stress. Several publications have demonstrated the importance of the autophagy process in the pathophysiology of dry age-related macular degeneration (AMD). Still, the mechanism underlying this process and its involvement in dry AMD are not fully characterized. Investigating the autophagy process in retinal pigment epithelial (RPE) cells, we identified transforming growth factor ß activated kinase 1 (TAK1) as a key player in the process. We found increased TAK1 phosphorylation in ARPE-19 and D407 cells treated with different inducers of autophagy, such as oxidative stress and rapamycin. Moreover, utilizing TAK1 specific inhibitor prior to oxidative stress or rapamycin treatment, we found significant reduction in LC3A/B-II expression. These results point at the involvement of TAK1 in the regulation of autophagy in RPE cells. This study suggests that aberrant activity of this kinase impairs autophagy and subsequently leads to alterations in the vitality of RPE cells. Proper activity of TAK1 may be essential for efficient autophagy, and crucial for the ability of RPE cells to respond to stress and dispose of damaged organelles, thus preventing or delaying retinal pathologies.

INTRAOCULAR PRESSURE IN PATIENTS WITH DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE INTRAVITREAL IMPLANT IN THE 3-YEAR MEAD STUDY.

PURPOSE: To evaluate the occurrence, management, and clinical significance of increases in intraocular pressure (IOP) in patients with diabetic macular edema treated with dexamethasone intravitreal implant (DEX implant). METHODS: Randomized, multicenter, 3-year, Phase III study. Patients (N = 1,048) with diabetic macular edema were randomized to DEX implant 0.7-mg, DEX implant 0.35-mg, or sham procedure with retreatment allowed at ≥6-month intervals (seven injections maximum). RESULTS: In the DEX implant 0.7-mg, DEX implant 0.35-mg, and sham groups, respectively, ≥10-mmHg IOP increases from baseline occurred in 27.7%, 24.8%, and 3.7% of patients, and their frequency did not increase with repeat injections. IOP-lowering medication was used by 41.5%, 37.6%, and 9.1% of patients. Only one patient (0.3%) in each DEX implant group had filtering surgery to manage a steroid-induced IOP increase. Among DEX implant 0.7-mg-treated patients with and without a ≥10-mmHg IOP increase, 21.9% (21 of 96) and 22.4% (57 of 255), respectively, achieved ≥15-letter best-corrected visual acuity gain at the end of the study, and mean average change in central retinal thickness from baseline was -127 µm and -106 µm, respectively. CONCLUSION: DEX implant demonstrated clear benefit of treatment despite increases in IOP. Sequential implants had no cumulative effect on IOP.

Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial.

PURPOSE: To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). PROCEDURES: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. RESULTS: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. CONCLUSION: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients.

TGF-ß1 induced transdifferentiation of rpe cells is mediated by TAK1.

BACKGROUND AND AIM: Proliferative vitreoretinopathy (PVR) is an active process that develops as a complication upon retinal detachment (RD), accompanied by formation of fibrotic tissue. The main cells involved in the development of fibrotic tissue during PVR are the retinal pigment epithelial (RPE) cells. The RPE cells undergo epithelial-mesenchymal transition (EMT) which leads to complex retinal detachment and loss of vision. Transforming growth factor-ß1 (TGF-ß1) is considered as the main player in the EMT of RPE cells, even though the mechanism is not fully understood. This study was performed to determine the possible involvement of transforming growth factor ß activated kinase 1 (TAK1) in the EMT process of the RPE cells. METHODOLOGY: ARPE-19 Cells were treated with 5Z-7 oxozeaenol (TAK1 inhibitor) or SB431542 (TGF-ß1 receptor kinase inhibitor) followed by TGF-ß1 stimulation. Immunofluorescence, scratch assay Real time PCR and collagen contraction assay assessed the EMT features. The phosphorylation of Smad2/3 and p38 was examined using western blots analysis. RESULTS: This study demonstrates that stimulation of RPE cells with TGF-ß1 increases α-SMA expression, cell migration and cell contractility, all of which are EMT features. Remarkably, addition of TAK1 inhibitor abolishes all these processes. Furthermore, we show hereby that TAK1 regulates not only the activation of the non-canonical cascade of TGF-ß1 (p38), but also the canonical cascade, the Smad2/3 activation. Thus, the outcome of the TGF-ß response in RPE cells is TAK1 dependent. CONCLUSIONS/SIGNIFICANCE: This work demonstrated TAK1, a component of the non-canonical pathway of TGF-ß1, is a key player in the EMT process, thus provides deep insight into the pathogenesis of PVR. The ability to halt the process of EMT in RPE cells may reduce the severity of the fibrotic response that occurs upon PVR, leading to a better prognosis and increase the probability of success in RD treatment.

TAK1 inhibition accelerates cellular senescence of retinal pigment epithelial cells.

PURPOSE: Oxidative stress and cellular senescence are known to contribute to the development of AMD; however, the mechanism is not fully understood. This study investigated the role of TGF-ß-activated kinase 1 (TAK1) in the senescence of RPE cells as a model for the development of dry AMD. METHODS: Cultured human RPE cells were treated with the TAK1 inhibitor 5Z-7-oxozeaenol for 1 hour, and then treated with 200 µM hydrogen peroxide for 1 hour. Human RPE cells that were not pretreated with TAK1 inhibitor for 1 hour served as controls. Senescence-associated ß-galactosidase (SA-ß-gal) activity was detected by histochemistry, and p53 expression by immunoblotting. Cell-cycle and apoptosis rate in RPE cells were determined by flow cytometry. RESULTS: The TAK1 expression in human RPE cells was high and was altered on oxidative stress. Transforming growth factor-ß-activated kinase 1 inhibition led to reduction in cell proliferation, cell-cycle arrest at G0/G1, and increased SA-ß-gal expression, all known to be features of cell senescence. Exposure of cells to oxidative stress combined with inhibition of TAK1 activity decreased the expression of apoptotic proteins, such as p53, and promoted cellular senescence. Aberrant TAK1 activity in RPE cells triggered their secretion of factors that induced hypertrophy and fibrotic changes in neighboring cells. CONCLUSIONS: The in vitro evidence indicated a role for TAK1 in the onset of senescence in RPE cells. The data shown hereby demonstrated that TAK1 activity is essential for maintaining normal function of RPE cells. Elucidation of its role in mechanisms underlying RPE cellular senescence induction may potentiate development of powerful tools for halting the development of dry AMD.

Contrast sensitivity, ocular blood flow and their potential role in assessing ischaemic retinal disease.

PURPOSE: To examine the definition, evaluation methodology, association to ocular blood flow and potential clinical value of contrast sensitivity (CS) testing in clinical and research settings, focusing in patients with ischemic retinal disease. METHODS: A review of the medical literature focusing on CS and ocular blood flow in ischemic retinal disease. RESULTS: CS may be more sensitive than other methods at detecting subtle defects or improvements in primarily central retinal ganglion cell function early on in a disease process. CS testing attempts to provide spatial detection differences which are not directly assessed with standard visual acuity chart testing. Analyzing all studies that have assessed both CS change and ocular blood flow, it is apparent that both choroidal circulation and retinal circulation may have an important role in influencing CS. CONCLUSION: The concept that CS is directly influenced by ocular blood flow is supported by reviewing the studies involving both. Although the studies in the literature have not established a direct cause and effect relationship per se, the literature review makes it logical to assume that changes in retinal and choroidal blood flow influence CS. This raises the possibility that a subjective visual characteristic, specifically CS, may be able to be evaluated more objectively by studying blood flow. It appears appropriate to study the relationship between blood flow and CS more extensively to develop improved ways of measuring various aspects of blood flow to the eye and to best quantify early changes in visual function.

Toward earlier detection of choroidal neovascularization secondary to age-related macular degeneration: multicenter evaluation of a preferential hyperacuity perimeter designed as a home device.

PURPOSE: The primary purpose of this study was to evaluate the ability of a home device preferential hyperacuity perimeter to discriminate between patients with choroidal neovascularization (CNV) and intermediate age-related macular degeneration (AMD), and the secondary purpose was to investigate the dependence of sensitivity on lesion characteristics. METHODS: All participants were tested with the home device in an unsupervised mode. The first part of this work was retrospective using tests performed by patients with intermediate AMD and newly diagnosed CNV. In the second part, the classifier was prospectively challenged with tests performed by patients with intermediate AMD and newly diagnosed CNV. The dependence of sensitivity on lesion characteristics was estimated with tests performed by patients with CNV of both parts. RESULTS: In 66 eyes with CNV and 65 eyes with intermediate AMD, both sensitivity and specificity were 0.85. In the retrospective part (34 CNV and 43 intermediate AMD), sensitivity and specificity were 0.85 +/- 0.12 (95% confidence interval) and 0.84 +/- 0.11 (95% confidence interval), respectively. In the prospective part (32 CNV and 22 intermediate AMD), sensitivity and specificity were 0.84 +/- 0.13 (95% confidence interval) and 0.86 +/- 0.14 (95% confidence interval), respectively. Chi-square analysis showed no dependence of sensitivity on type (P = 0.44), location (P = 0.243), or size (P = 0.73) of the CNV lesions. CONCLUSION: A home device preferential hyperacuity perimeter has good sensitivity and specificity in discriminating between patients with newly diagnosed CNV and intermediate AMD. Sensitivity is not dependent on lesion characteristics.

Early OCT changes of neuroretinal foveal thickness after first versus repeated PDT in AMD.

PURPOSE: To compare early optical coherence tomography (OCT) changes in neuroretinal foveal thickness (NFT) after first versus repeated photodynamic treatment (PDT) in eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: This is a prospective comparative case series study. Consecutive AMD patients, treated with PDT due to subfoveal CNV, were enrolled. The eyes were divided into two groups: group A included eyes that had received the first initial treatment, and group B included eyes that had received repeated treatment. All eyes underwent serial examinations with OCT: prior to PDT, 1 h, and 3 months after the PDT. The primary outcome measure was early OCT change in NFT after PDT. RESULTS: Thirty-three eyes of 33 patients were included in this study; 16 in group A and 17 in group B. Optical coherence tomography showed a significant increase in NFT 1 h after PDT, as compared to pre-treatment status, in group A eyes (P = 0.008) but not in group B eyes (P = 0.731). Subretinal fluid was increased in both groups (93.8% and 88.2%, respectively), whereas intraretinal fluid was remarkably more increased in group A eyes (88%) than in group B eyes (59%). CONCLUSION: Early change in NFT, demonstrated on OCT, indicates that PDT causes different retinal response in primary versus repeated treatment of PDT for CNV due to AMD.

Weekly vaccination with Copaxone (glatiramer acetate) as a potential therapy for dry age-related macular degeneration.

PURPOSE: Drusen formation in age-related macular degeneration (AMD) shares some similarities with Alzheimer's disease (AD), which is associated with amyloid deposits. Aggregated beta-amyloid induces microglia to become cytotoxic and block neurogenesis. Recent evidence showed that T cell-based vaccination with Copaxone in AD mice model resulted in modulation of microglia into neuroprotective phenotype and as a result in reduction of cognitive decline, elimination of plaque formation, and induction of neuronal survival and neurogenesis. The aim was to investigate whether the effect of Copaxone on drusen in dry AMD is similar to that on deposits of other age-related chronic neurodegenerative diseases such as Alzheimer disease (AD). MATERIALS AND METHODS: Patients over 50 years of age with intermediate dry AMD in both eyes were randomized to receive Copaxone or sham injections and were weekly treated by subcutaneous injections of Copaxone (dose of 20 mg) or sham injections for 12 weeks. At baseline, 6-week, and 12-week visits, visual acuity, contrast sensitivity, fundus examination and photography, fluorescein angiography, and ocular coherent tomography were performed. Main outcome measure was a change in total drusen area (TDA) measured by Image-Pro software and presented in arbitrary units (AU). RESULTS: Eight studied eyes of four treated patients showed a decrease in TDA from 48130 to 16205 AU at 12 weeks as compared to baseline. In contrast, four control eyes (two patients) demonstrated almost no change in TDA (from 32294 to 32781 AU). CONCLUSION: These preliminary results show that Copaxone reduces drusen area.