Macular Degeneration: Patel M

Ding X, Patel M, Chan CC. · Immunopathology Section, Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892-1857, USA. · Prog Retin Eye Res. · Pubmed #19026761 links to  free full text

Abstract: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch's membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress.

Patel M, Chan CC. · Section of Immunopathology, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, 10/10N103, NIH/NEI, Bethesda, MD 20892-1857, USA. · Semin Immunopathol. · Pubmed #18299834 links to  free full text

Abstract: Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and beneath the retinal pigment epithelium, recruitment of macrophages for clearance of these deposits, complement activation, recruitment of tissue-destructive macrophages, microglial activation and accumulation, and proinflammatory effects of chronic inflammation by Chlamydia pneumoniae. This review discusses the evidence for the role of inflammation in human AMD and in animal models of AMD.

Starita C, Patel M, Katz B, Adamis AP. · Pfizer Ltd., Sandwich, UK. · Dev Ophthalmol. · Pubmed #17245083 No free full text.

Abstract: Both clinical and preclinical findings have implicated vascular endothelial growth factor (VEGF) in the pathophysiology of diabetic macular edema (DME). VEGF is both a potent enhancer of vascular permeability and a key inducer of angiogenesis. VEGF levels are elevated in the eyes of patients with DME, and in animal models of diabetes this elevation coincides with the breakdown of the blood-retinal barrier. Moreover, injection of VEGF (the VEGF165 isoform in particular) into healthy eyes of animals can induce diabetes-associated ocular pathologies.Pegaptanib, a novel RNA aptamer currently used in the treatment of agerelated macular degeneration, binds and inactivates VEGF165 and has been shown in animal models to reverse the blood-retinal barrier breakdown associated with diabetes. These findings formed the basis of a phase II trial involving 172 patients with DME, in which intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections were administered every 6 weeks for 12 weeks, with the option of continuing for 18 more weeks or undergoing laser treatment. Compared to sham, patients receiving 0.3 mg displayed superior visual acuity (p = 0.04) as well as a reduction in retinal thickness of 68 micrometers compared to a slight increase under sham treatment (p = 0.021). These data support the use of pegaptanib in the treatment of DME.

Anonymous00151, Apte RS, Modi M, Masonson H, Patel M, Whitfield L, Adamis AP. · Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110, USA. · Ophthalmology. · Pubmed #17509689 No free full text.

Abstract: OBJECTIVE: To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib sodium in subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN: Prospective 2-cohort study: (1) open-label cohort and (2) randomized, double-masked, uncontrolled multicenter trial. PARTICIPANTS: In the combined cohorts, 147 subjects with any angiographic subtype of subfoveal choroidal neovascularization secondary to AMD and best-corrected visual acuities (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or better received pegaptanib sodium. INTERVENTION: Subjects were randomized to receive intravitreous pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than the 0.3-mg approved dose]) every 6 weeks for 54 weeks. MAIN OUTCOME MEASURES: Safety assessments included blood chemistries, urinalyses, vital signs, electrocardiograms, serum antipegaptanib antibody assays, adverse events, VAs, and intraocular pressures. After the first, fourth, and eighth injections, serial blood samples were obtained for quantification of pegaptanib plasma concentrations. RESULTS: No antipegaptanib immunoglobulin G (IgG) or IgM antibodies were detected. Few systemic adverse events were noted. Mild or moderate ocular adverse events related to the injection procedure were reported in most patients. Pegaptanib did not accumulate in plasma after multiple doses; systemic exposures were similar after the first, fourth, and eighth doses. The mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP) and urine protein, both of which are known to be affected by systemic VEGF inhibition, indicated no evidence of a pegaptanib treatment effect on these parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and 90 mmHg (diastolic), levels considered hypertension by the American College of Cardiology. CONCLUSIONS: At doses up to 10-fold higher than the 0.3-mg dose approved for the treatment of AMD, pegaptanib sodium was well tolerated, with no detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically meaningful changes in proteinuria or mean BP) and no clinically relevant ocular inflammation. Most ocular adverse events were related to the injection procedure itself and were mild or moderate in severity.

Cunningham ET, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD, Anonymous00243. · Stanford University, USA. · Ophthalmology. · Pubmed #16154196 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and efficacy of pegaptanib sodium injection (pegaptanib) in the treatment of diabetic macular edema (DME). DESIGN: Randomized, double-masked, multicenter, dose-ranging, controlled trial. PARTICIPANTS: Individuals with a best-corrected visual acuity (VA) between 20/50 and 20/320 in the study eye and DME involving the center of the macula for whom the investigator judged photocoagulation could be safely withheld for 16 weeks. INTERVENTION: Intravitreous pegaptanib (0.3 mg, 1 mg, 3 mg) or sham injections at study entry, week 6, and week 12 with additional injections and/or focal photocoagulation as needed for another 18 weeks. Final assessments were conducted at week 36. MAIN OUTCOME MEASURES: Best-corrected VA, central retinal thickness at the center point of the central subfield as assessed by optical coherence tomography measurement, and additional therapy with photocoagulation between weeks 12 and 36. RESULTS: One hundred seventy-two patients appeared balanced for baseline demographic and ocular characteristics. Median VA was better at week 36 with 0.3 mg (20/50), as compared with sham (20/63) (P = 0.04). A larger proportion of those receiving 0.3 mg gained VAs of > or =10 letters (approximately 2 lines) (34% vs. 10%, P = 0.003) and > or =15 letters (18% vs. 7%, P = 0.12). Mean central retinal thickness decreased by 68 microm with 0.3 mg, versus an increase of 4 microm with sham (P = 0.02). Larger proportions of those receiving 0.3 mg had an absolute decrease of both > or =100 microm (42% vs. 16%, P = 0.02) and > or =75 microm (49% vs. 19%, P = 0.008). Photocoagulation was deemed necessary in fewer subjects in each pegaptanib arm (0.3 mg vs. sham, 25% vs. 48%; P = 0.04). All pegaptanib doses were well tolerated. Endophthalmitis occurred in 1 of 652 injections (0.15%/injection; i.e., 1/130 [0.8%] pegaptanib subjects) and was not associated with severe visual loss. CONCLUSIONS: In this phase II trial, subjects assigned to pegaptanib had better VA outcomes, were more likely to show reduction in central retinal thickness, and were deemed less likely to need additional therapy with photocoagulation at follow-up.

Shen D, Tuo J, Patel M, Herzlich AA, Ding X, Chew EY, Chan CC. · 10 Center Drive, 10/10N103, National Institutes of Health/National Eye Institute, Bethesda, MD 20892-1857, USA. · Br J Ophthalmol. · Pubmed #18996904 No free full text.

Abstract: BACKGROUND/AIMS: Impaired inhibition of the alternative complement pathway by complement factor H (CFH) is linked to age-related macular degeneration (AMD) based on the strong association between CFH variant and AMD. Chlamydia pneumoniae (C pneumoniae) infection can trigger the alternative pathway, but the evidence for an association between C pneumoniae and AMD is contradictory. This study investigated whether C pneumoniae infection is associated with AMD and whether the presence of C pneumonia modulates AMD risk conferred by CFH variants. METHODS: Genomic DNA extracted from peripheral blood of 148 advanced AMD patients and 162 controls was subjected to Taqman and PCR-RFLP for the CFH polymorphism and PCR for the C pneumoniae gene. Genomic DNA was also examined from microdissected macular cells from 59 AMD and 16 age-matched non-AMD archived slides. chi(2) testing was performed for case-control analysis. RESULTS: C pneumoniae infection was associated with increased risk of AMD (OR = 2.17, p<0.017). A CFH variant was also linked to increased risk of AMD (OR = 1.98, p<0.0001). However, no relationship was found between risk-conferring CFH variant and C pneumoniae (OR = 1.81, p = 0.08). CONCLUSION: There is a possible association between AMD and C pneumoniae infection, although CFH may not be directly involved in the pathogenesis of C pneumoniae infection-mediated AMD.

Singerman LJ, Masonson H, Patel M, Adamis AP, Buggage R, Cunningham E, Goldbaum M, Katz B, Guyer D. · Retina Associates of Cleveland, 3401 Enterprise Parkway, Suite 300, Cleveland, OH 44122, USA. · Br J Ophthalmol. · Pubmed #18614570 links to  free full text

Abstract: AIMS: To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). METHODS: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. RESULTS: As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment. CONCLUSION: The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.

Foy JW, Rittenhouse K, Modi M, Patel M. · (OSI) Pharmaceuticals, Boulder, CO 80301, USA. · J Ocul Pharmacol Ther. · Pubmed #17900226 No free full text.

Abstract: PURPOSE: To evaluate the local tolerance, systemic toxicity, and toxicokinetics in dogs and rabbits of pegaptanib sodium, an aptamer that targets vascular endothelial growth factor (VEGF(165)). METHODS: Dogs received biweekly, bilateral, intravitreous (IVT) injections of pegaptanib sodium for 9 months at doses of 0.3 (n = 10), 1 (n = 10), or 3 mg (n = 14); 14 control dogs received phosphate-buffered saline (PBS). In rabbits, pegaptanib sodium was administered by IVT injection biweekly for 6 months at doses of 0.2 (n = 14), 0.67 (n = 14), or 2 mg (n = 18); 18 rabbits received PBS. The systemic and ocular safety of pegaptanib sodium was assessed. Assessments in both dogs and rabbits included complete ophthalmologic examinations, serum chemistry, hematology, urinalysis, and coagulation assessments, as well as gross and microscopic pathologic examination. In addition, dogs were assessed by electroretinography and electrocardiography. In a cardiovascular safety study, loading intravenous boluses and maintenance infusions of pegaptanib sodium or PBS were administered to dogs (n = 4) in an ascending dose design, with each dose level separated by 2-3 days. The pegaptanib dosing regimens were designed to achieve pegaptanib plasma concentrations of approximately 90, 270, or 900 ng/mL. RESULTS: There were no pegaptanib sodium-associated clinical, ophthalmologic, pathologic, or cardiovascular abnormalities at doses of pegaptanib that achieved systemic and ocular exposure levels in excess of those associated with the recommended pegaptanib IVT dosing regimen of 0.3 mg per study eye in patients with age-related macular degeneration. CONCLUSION: These studies, together with data from clinical trials, provide strong evidence that inhibition of VEGF(165) by pegaptanib in the eye is a safe therapy for the treatment of ocular neovascular disease.

Leys A, Zlateva G, Shah SN, Patel M. · Department of Opthalmology, University Hospital Leuven, Leuven, Belgium. · Eye. · Pubmed #17585313 No free full text.

Abstract: PURPOSE: To assess the impact of treatment with pegaptanib sodium vs usual care on vision-related quality of life (VRQoL) in patients with age-related macular degeneration (AMD). METHODS: VRQoL was a secondary end point in the trial, a prospective, randomized, double-masked, multicentre, dose-ranging study. Three doses of pegaptanib (0.3, 1, and 3 mg) were compared with usual care with respect to changes in VRQoL as indicated by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25), administered at baseline and weeks 30 and 54. Four of the NEI-VFQ 25 domains were prospectively designated as primary: near vision, distance vision, role limitations, and dependency. Between-group differences were assessed using an analysis of covariance model with age, gender, and baseline score as covariates. RESULTS: NEI-VFQ 25 data were available for 569 subjects. At week 54, improvements in the distance vision and role limitations domains were greater in pegaptanib than usual care arms. No substantial increase in ocular pain was noted in pegaptanib-treated patients. No clear superiority of any particular dosage strength of pegaptanib was demonstrated, and no significant differences or trends favoured usual care on any domain score or the NEI-VFQ 25 composite score. The greatest VRQoL benefit was seen in responders (lost<3 lines) to treatment. CONCLUSION: The VISION trial provided evidence of trends in quality-of-life benefit associated with effective treatment of AMD using pegaptanib. Treatment with pegaptanib is expected to contribute significantly to VRQoL improvement for responder patients.

Duan Y, Mo J, Klein R, Scott IU, Lin HM, Caulfield J, Patel M, Liao D. · Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. · Ophthalmology. · Pubmed #17187863 No free full text.

Abstract: OBJECTIVE: To investigate whether age-related macular degeneration (AMD) is associated with the development of myocardial infarction (MI) among elderly Americans. DESIGN: Population-based cross-sectional and cohort study. PARTICIPANTS: Five percent random sample of 2000 to 2003 Medicare enrollees. METHODS: The cross-sectional study included the first 2-year (2000 and 2001) enrollees who were aged > or =65 years (n = 1,519,086). The cohort study included only baseline MI-free enrollees (n = 1445677). MAIN OUTCOME MEASURES: Chronic conditions (AMD and type, history of MI, hypertension, and diabetes) were defined based on any occurrence of relevant International Classification of Diseases 9 codes in relevant diagnosis fields of the baseline Medicare claim files. A total of 56611 incident MI cases were identified from the follow-up data (2002 and 2003). RESULTS: Baseline mean age was 76 years, with 60% women and 88% whites. The prevalence of neovascular AMD was 2.2% (2.3% in women vs. 1.7% in men and 2.3% in whites vs. 1.2% in blacks; P<0.01 for both gender and race differences). The prevalence of nonneovascular AMD was 8.8% (9.9% in women vs. 7.3% in men and 9.5% in whites vs. 4.3% in blacks; P<0.01 for both gender and race differences). Baseline age-, gender-, and race-adjusted prevalences of hypertension, diabetes, and history of MI were 75%, 33%, and 5.00%, respectively, in the neovascular AMD group. In contrast, they were 73%, 27%, and 4.68% in the nonneovascular AMD group, and 65%, 25%, and 4.54% in the non-AMD group (P<0.01 for comparing the prevalence in neovascular and nonneovascular AMD vs. non-AMD groups). Prospectively, baseline age-, gender-, race-, hypertension-, and diabetes-adjusted 2-year incident odds ratios and 95% confidence intervals of MI associated with AMD are 1.19 (1.16-1.22) for all persons with AMD, 1.26 (1.20-1.33) for neovascular AMD, and 1.18 (1.14-1.21) for nonneovascular AMD. CONCLUSIONS: AMD is associated with older age, female gender, being white, and having a history of MI, hypertension, and diabetes. Furthermore, presence of AMD, especially neovascular AMD, is prospectively associated with a higher risk of incident MI. These findings, if confirmed by other studies that control for smoking and other lifestyle covariables, suggest the possibility of shared common antecedents between MI and AMD.

Anonymous00326, Chakravarthy U, Adamis AP, Cunningham ET, Goldbaum M, Guyer DR, Katz B, Patel M. · Centre for Vision Sciences, The Queen's University of Belfast and The Royal Victoria Hospital, Belfast, United Kingdom. · Ophthalmology. · Pubmed #16828500 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in patients who were randomized to receive therapy with pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.

Anonymous00201, D'Amico DJ, Masonson HN, Patel M, Adamis AP, Cunningham ET, Guyer DR, Katz B. · Department of Ophthalmology, Harvard Medical School, Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. · Ophthalmology. · Pubmed #16647134 No free full text.

Abstract: OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. METHODS: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. RESULTS: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for >1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD.

Shah SP, Patel M, Thomas D, Aldington S, Laidlaw DA. · London School of Hygiene and Tropical Medicine, UK. · Br J Ophthalmol. · Pubmed #16361663 links to  free full text

Abstract: AIM: To determine preoperative demographic, clinical, and optical coherence tomography (OCT) factors which might predict the visual and anatomical outcome at 1 year in patients undergoing vitrectomy and inner limiting membrane peel for diabetic macular oedema (DMO). METHODS: A prospective, interventional case series of 33 patients who completed 1 year follow up. Measurements were taken preoperatively and at 1 year. Outcome measures were logMAR visual acuity (VA) and OCT macular thickness. A priori explanatory variables included baseline presence of clinical and/or OCT signs suggesting macular traction, grade of diabetic maculopathy, posterior vitreous detachment, fluorescein leakage and ischaemia on angiography, presence of subretinal fluid, and peroperative indocyanine green (ICG) use. RESULTS: 33 patients completed 1 year follow up. On average VA deteriorated by 0.035 logMAR (p = 0.40). Macular thickness significantly improved by a mean of 139 microm (95% CI; 211 to 67, p<0.001). Patients with evidence of clinical and/or OCT macular traction significantly improved logMAR acuity (logMAR improvement = 0.08) compared with patients without traction (logMAR deterioration 0.11, p = 0.01). Presence of subretinal fluid significantly predicted worse postoperative result (p = 0.01) CONCLUSION: On average, patients showed a statistically significant improvement in central macular thickness following treatment but a marginal acuity worsening. Presence of subretinal fluid on OCT is hypothesised to be exudative rather than tractional in nature. The visual benefit of vitrectomy for DMO in this study was limited to patients who exhibit signs of macular traction either clinically and/or on OCT.

Adamis AP, Altaweel M, Bressler NM, Cunningham ET, Davis MD, Goldbaum M, Gonzales C, Guyer DR, Barrett K, Patel M, Anonymous00106. · No affiliation provided · Ophthalmology. · Pubmed #16343627 No free full text.

Abstract: OBJECTIVE: To study effects of intravitreal pegaptanib (Macugen) on retinal neovascularization. DESIGN: Retrospective analysis of a randomized clinical trial. PARTICIPANTS, INTERVENTION, AND MAIN OUTCOME MEASURES: Individuals with retinal neovascularization identified from a multicenter, randomized, controlled trial evaluating pegaptanib for treatment of diabetic macular edema, with a best-corrected visual acuity letter score between 68 and 25 (approximate Snellen equivalent between 20/50 and 20/320) and receiving a sham injection or intravitreal pegaptanib (0.3 mg, 1 mg, 3 mg) administered at study entry, week 6, and week 12, with additional injections and/or focal photocoagulation as needed during the ensuing 18 weeks, up to a maximum of 6 pegaptanib/sham therapies, were evaluated. Scatter panretinal photocoagulation before study enrollment was permitted, but not within 6 months of randomization and study entry. Changes in retinal neovascularization were assessed on fundus photographs and fluorescein angiograms graded at a reading center in a masked fashion. RESULTS: Of 172 participants, 19 had retinal neovascularization in the study eye at baseline. Excluding 1 who had scatter photocoagulation 13 days before randomization and 2 with no follow-up photographs, 1 of the remaining 16 subjects had panretinal photocoagulation during study follow-up. Of these 16 subjects, 8 of 13 (62%) in a pegaptanib treatment group (including the one receiving panretinal photocoagulation), 0 of 3 in the sham group, and 0 of 4 fellow (nonstudy) eyes showed either regression of neovascularization on fundus photographs or regression or absence of fluorescein leakage from neovascularization (or both) at 36 weeks. In 3 of 8 with regression, neovascularization progressed at week 52 after cessation of pegaptanib at week 30. CONCLUSIONS: Most subjects with retinal neovascularization at baseline assigned to pegaptanib showed regression of neovascularization by week 36. These findings suggest a direct effect of pegaptanib upon retinal neovascularization in patients with diabetes mellitus.