Macular Degeneration: Nguyen QD

Do DV, Nguyen QD, Shah SM, Browning DJ, Haller JA, Chu K, Yang K, Cedarbaum JM, Vitti RL, Ingerman A, Campochiaro PA. · The Wilmer Eye Institute, 600 North Wolfe Street, Maumenee #719, Baltimore, MD 21287, USA. · Br J Ophthalmol. · Pubmed #19174400 No free full text.

Abstract: AIM: The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO). METHODS: Five subjects with DMO, foveal thickness > or =250 microm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT. RESULTS: Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 microm. At 4 weeks after injection, the median excess FTH was 59 microm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 microm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters). CONCLUSIONS: A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.

Nguyen QD, Shah SM, Hafiz G, Do DV, Haller JA, Pili R, Zimmer-Galler IE, Janjua K, Symons RC, Campochiaro PA. · Department of Ophthalmology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. · Am J Ophthalmol. · Pubmed #18054887 No free full text.

Abstract: PURPOSE: To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. DESIGN: Nonrandomized clinical trial. METHODS: Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. RESULTS: Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 mum representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. CONCLUSIONS: Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV.

Shah SM, Tatlipinar S, Quinlan E, Sung JU, Tabandeh H, Nguyen QD, Fahmy AS, Zimmer-Galler I, Symons RC, Cedarbaum JM, Campochiaro PA. · Retinal Imaging Research and Reading Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. · Invest Ophthalmol Vis Sci. · Pubmed #17122137 links to  free full text

Abstract: PURPOSE: In this study, the authors sought to develop and characterize techniques for measuring changes in choroidal neovascularization (CNV) lesion size and fluorescence over time for quantitative analysis of fluorescein angiograms. METHODS: Initial assessment of the quantitative technique was made by retrospectively analyzing digital fluorescein angiograms taken before and 3 months after photodynamic therapy (PDT) for CNV (6 patients, group 1). The method was then applied prospectively to digital fluorescein angiograms (baseline and day 71) obtained on 12 patients taking part in a clinical trial investigating the effect of vascular endothelial growth factor (VEGF) Trap in CNV (group 2). Two masked observers, with the use of image processing, measured the area of hyperfluorescence and fluorescence intensity above background. Values for each image were plotted against time after dye injection to generate curves, and each area under the curve (AUC) was calculated. RESULTS: The physician who treated the patients in group 1 judged the condition of three patients to be improved and of three to be worse 3 months after PDT. Masked retrospective grading of fluorescein angiograms showed an 11% decrease in AUC for fluorescence area and a 32% decrease in AUC for fluorescence intensity in the three patients whose conditions clinically improved but increases of 131% and 292% in the three patients whose conditions clinically worsened. In group 2, a 38% decrease in AUC for fluorescence intensity and a 19% decrease in AUC for fluorescence area were observed in patients who received VEGF Trap compared with increases of 66% (P = 0.004, Mann-Whitney U test) and 21% (P = 0.07) for patients who received placebo. Macular volume decreased by 11% in VEGF Trap-treated patients and increased by 10% in placebo-treated patients (P = 0.03). CONCLUSIONS: This study reports a technique for analysis of change in fluorescence area and intensity over time during fluorescein angiography (FA) using a continuous scale and its application in a clinical setting and a clinical trial. Compared with previous techniques making use of categorical scales, this approach provides an advantage for evaluating responses to treatment that may improve the value of FA as an outcome measure in clinical trials.

Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J, Zimmer-Galler I, Do DV, Campochiaro PA. · The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. · Am J Ophthalmol. · Pubmed #17046701 No free full text.

Abstract: PURPOSE: The role of vascular endothelial growth factor (VEGF) in diabetic macular edema (DME) was tested with ranibizumab, a specific antagonist of VEGF. DESIGN: A nonrandomized clinical trial. METHODS: Ten patients with chronic DME received intraocular injections of 0.5 mg of ranibizumab at baseline and at one, two, four, and six months. The primary outcome was change in foveal thickness between baseline and seven months, and the secondary outcome measures were changes from baseline in visual acuity and macular volume. RESULTS: Mean values at baseline were 503 microm for foveal thickness, 9.22 mm3 for macular volume, and 28.1 letters (20/80) read on an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. At seven months (one month after the fifth injection), the mean foveal thickness was 257 microm, which was a reduction of 246 microm (85% of the excess foveal thickness present at baseline; P = .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance). The macular volume was 7.47 mm3, which was a reduction of 1.75 mm3 (77% of the excess macular volume at baseline; P = .009). Mean visual acuity was 40.4 letters (20/40), which was an improvement of 12.3 letters (P = .005). The injections were well-tolerated with no ocular or systemic adverse events. CONCLUSION: Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME, which demonstrated that VEGF is an important therapeutic target for DME. A randomized, controlled, double-masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME.

Nguyen QD, Shah SM, Hafiz G, Quinlan E, Sung J, Chu K, Cedarbaum JM, Campochiaro PA, Anonymous00330. · Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland MD 21287-9277, USA. · Ophthalmology. · Pubmed #16876249 No free full text.

Abstract: OBJECTIVES: To assess the safety, pharmacokinetics, and biological activity of IV administration of vascular endothelial growth factor trap (VEGF Trap), a recombinant protein containing the binding domains of VEGF receptors 1 and 2, in patients with neovascular age-related macular degeneration (AMD). DESIGN: Randomized, multicenter, placebo-controlled clinical trial. PARTICIPANTS: Twenty-five patients were enrolled (11 male, 14 female); 19 received VEGF Trap (0.3 [n = 7], 1.0 [n = 7], or 3.0 mg/kg [n = 5]), and 6 received a placebo. METHODS: Patients were randomized to receive a placebo or 0.3-, 1.0-, or 3.0-mg/kg VEGF Trap--a single IV dose followed by a 4-week observation period and then 3 doses 2 weeks apart. MAIN OUTCOME MEASURES: Safety and biological activity, including change in excess retinal thickness and volume assessed by optical coherence tomography and visual acuity (VA) measured by the Early Treatment Diabetic Retinopathy Study protocol. RESULTS: The majority of adverse events attributable to VEGF Trap were mild to moderate in severity, but 2 of 5 patients treated with 3.0 mg/kg experienced dose-limiting toxicity (1 with grade 4 hypertension and 1 with grade 2 proteinuria); therefore, all patients in the 3.0 mg/kg-dose group were withdrawn from the study. The mean percent changes in excess retinal thickness were -12%, -10%, -66%, and -60%, respectively, for the placebo and 0.3-, 1.0-, and 3.0-mg/kg groups at day 15 (P<0.02 by analysis of covariance [ANCOVA]) and -5.6%, +47.1%, and -63.3% for the placebo and 0.3- and 1.0-mg/kg groups at day 71 (P<0.02, ANCOVA). A significant change in VA was not noted in this small study. CONCLUSIONS: The maximum tolerated dose of IV VEGF Trap in this study population was 1.0 mg/kg. This dose resulted in elimination of about 60% of excess retinal thickness after either single or multiple administrations. Alternative routes of delivery to increase the therapeutic window are being explored.

Campochiaro PA, Nguyen QD, Shah SM, Klein ML, Holz E, Frank RN, Saperstein DA, Gupta A, Stout JT, Macko J, DiBartolomeo R, Wei LL. · Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · Hum Gene Ther. · Pubmed #16454650 No free full text.

Abstract: Twenty-eight patients with advanced neovascular age-related macular degeneration (AMD) were given a single intravitreous injection of an E1-, partial E3-, E4-deleted adenoviral vector expressing human pigment epithelium- derived factor (AdPEDF.11). Doses ranging from 10(6) to 10(9.5) particle units (PU) were investigated. There were no serious adverse events related to AdPEDF.11 and no dose-limiting toxicities. Signs of mild, transient intraocular inflammation occurred in 25% of patients, but there was no severe inflammation. Six patients experienced increased intraocular pressure that was easily controlled by topical medication. All adenoviral cultures were negative. At 3 and 6 months after injection, 55 and 50%, respectively, of patients treated with 10(6)-10(7.5) PU and 94 and 71% of patients treated with 10(8)-10(9.5) PU had no change or improvement in lesion size from baseline. The median increase in lesion size at 6 and 12 months was 0.5 and 1.0 disk areas in the low-dose group compared with 0 and 0 disk areas in the high-dose group. These data suggest the possibility of antiangiogenic activity that may last for several months after a single intravitreous injection of doses greater than 10(8) PU of AdPEDF.11. This study provides evidence that adenoviral vector-mediated ocular gene transfer is a viable approach for the treatment of ocular disorders and that further studies investigating the efficacy of AdPEDF.11 in patients with neovascular AMD should be performed.

Nguyen QD, Shah SM, Van Anden E, Sung JU, Vitale S, Campochiaro PA. · Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. · Invest Ophthalmol Vis Sci. · Pubmed #14744906 links to  free full text

Abstract: PURPOSE: Diabetic macular edema (DME) is the most common cause of moderate visual disability in persons of working age in the United States. The pathogenesis of DME is poorly understood. In this study, the effect of retinal hypoxia in the development and maintenance of DME was investigated. METHODS: Five patients with chronic DME despite at least one focal laser photocoagulation treatment (nine eyes) received 4 L/min of inspired oxygen by nasal cannula for 3 months. Best corrected visual acuity (VA) and retinal thickness, assessed by optical coherence tomography (OCT), were measured at baseline, during 3 months of oxygen treatment, and for 3 months after stopping oxygen. RESULTS: After 3 months of oxygen therapy, nine of nine eyes with DME at baseline showed a reduction in thickness of the center of the macula. Foveal thickness (FTH) above the normal range was reduced by an average of 43.5% (range, 14%-100%), excess foveolar thickness (CEN) was reduced by an average of 42.1% (range, 13%-100%), and excess macular volume was reduced by an average of 54% (range, 35%-100%). Statistical analyses suggested that these changes were unlikely to be due to chance (P = 0.0077 by Wilcoxon signed-rank test). Three eyes showed improvement in VA by at least 2 lines, one by slightly less than 2 lines, and five eyes showed no change. Three months after discontinuation of oxygen, five of the nine eyes showed increased thickening of the macula compared with when oxygen was discontinued. CONCLUSIONS: Supplemental inspired oxygen may decrease macular thickness due to DME, suggesting that retinal hypoxia is involved in the development and maintenance of DME.

Rasmussen H, Chu KW, Campochiaro P, Gehlbach PL, Haller JA, Handa JT, Nguyen QD, Sung JU. · Clinical Research & Regulatory Affairs, USA. · Hum Gene Ther. · Pubmed #11727737 No free full text.

Abstract: Age-Related Macular Degeneration (AMD) is, together with Diabetic Retinopathy, the most common cause of vision loss among adults in the U.S. and other developed countries. In the U.S., at least 1.7 million people have impaired vision due to AMD. Every year, more than 165,000 people contract AMD and 16,000 go blind from it, predominantly from a rapidly progressing form of the disease called "wet" AMD. Wet AMD is characterized by serious or hemorrhagic detachment of the retinal pigment epithelium and choroidal neovascularization. The macula has the highest concentration of photoreceptors facilitating central vision and permitting high-resolution visual acuity. The damage caused by the leakage and fibrovascular scarring in wet AMD leads to profound loss of central vision and severe loss of visual acuity (usually 20/200 or worse). People with wet AMD have several limitations, including inability to read, inability to recognize faces or drive, and the disease often leads to blindness. The onset of severe visual changes in wet AMD can occur suddenly. More than 400,000 Americans are currently affected by this form of the disease, and the incidence is rising rapidly with the aging of the population. Therefore, the serious consequences of this disease along with the limited treatment options and their effectiveness make this a very good candidate for a gene transfer treatment approach. The investigational agent, Ad(GV)PEDF.11D, is an E1-, partial E3-, E4- deleted replication-deficient, adenovirus serotype 5, gene transfer vector. The transgene in this vector is the cDNA for human pigment epithelium-derived factor (PEDF). PEDF is one of the most potent known antiangiogenic proteins found in humans. While Ad(GV)PEDF.11D is able to transduce many somatic cell types, the natural barrier to other tissues created by the retina limits the ability of Ad(GV)PEDF.11D to affect tissues other than in the eye. Intravitreal administration of Ad(GV)PEDF.11D provides a convenient means of delivering PEDF to the relevant cells within the eye likely to result in a more prolonged duration of effect versus administration of the PEDF protein alone. In three murine disease models (the laser-induced choroidal neovascularization model, the VEGF transgenic model, and the retinopathy of prematurity model) significant inhibition of neovascularization (up to 85%) was demonstrated with doses of Ad(GV)PEDF vectors ranging from 1 x 10(8) to 1 x 10(9) pu. In toxicology studies performed in Cynomolgus monkeys, a dose-related inflammatory response was observed. A dose of 1 x 10(8) pu caused no adverse effects, while the inflammatory response observed at 1 x 10(9) pu was minimal and fully reversible. The observed inflammatory response at doses of 1 x 10(10) and 5 x 10(10) pu were increasingly severe. The proposed clinical trial is an open-label, dose-escalation, phase I study to investigate the safety, tolerability and potential activity of intravitreal injection of Ad(GV)PEDF.11D in patients with wet AMD. Ad(GV)PEDF.11D will be injected once via intravitreal injection into the eye with the most advanced AMD based on visual acuity. Subjects will be age 50 or over and have severe wet AMD in at least one eye defined by a best-corrected vision of 20/200 or worse. The primary objectives of this investigation are: (1) to assess the safety, tolerability and feasibility of intravitreal injection of Ad(GV)PEDF.11D in patients with severe, neovascular AMD, (2) to identify the maximum tolerated dose (MTD) of Ad(GV)PEDF.11D, and (3) to get some indication of potential activity of Ad(GV)PEDF.11D.

Khurana RN, Do DV, Nguyen QD. · Johns Hopkins Hospital, Wilmer Eye Institute, 600 North Wolfe Street, Maumenee 7th Floor, Baltimore, MD 21287, USA. · Int Ophthalmol Clin. · Pubmed #19349791 No free full text.

This publication has no abstract.

Lim LL, Scarborough JD, Thorne JE, Graham E, Kempen JH, Mackensen F, Nguyen QD, Prabriputaloong T, Read RW, Suhler EB, Schwartz JM, Smith JR. · Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. · Am J Ophthalmol. · Pubmed #19166713 No free full text.

Abstract: PURPOSE: To report seven cases of uveitis occurring in patients with autoimmune hepatitis (AIH), raising the possibility that uveitis may be an extrahepatic feature of AIH. DESIGN: Multicenter, retrospective, observational case series of patients with AIH and uveitis. METHODS: One index case was identified at Oregon Health & Science University. Further cases were identified by a web-based survey of members of the American Uveitis Society, the International Uveitis Study Group, the Proctor Foundation mailing list server, and the First SUN International Workshop. Respondents were asked to provide clinical information about uveitis phenotype, AIH features, and treatment. RESULTS: Clinical information was obtained for seven individuals (four females and three males; age range, seven to 67 years) who suffered from AIH and uveitis. Average duration of follow-up was 5.5 years. All patients had chronic, persistent bilateral uveitis that was anterior (n = 3), intermediate (n = 1), or pan (n = 3) in location. Every patient had complications arising from his or her uveitis, including cataract (n = 5), glaucoma (n = 3), cystoid macular edema (n = 3), and posterior synechiae (n = 3). Final visual acuities ranged from 20/16 to hand movements. To treat the uveitis and/or AIH, the majority of patients required oral prednisone and all seven patients were treated with systemic immunosuppression. CONCLUSION: Despite the small size of this study, our findings suggest an association between AIH and uveitis. The uveitis is chronic, bilateral, and associated with sight-threatening complications, necessitating systemic immunosuppression in some individuals.

Patel SJ, Petrarca R, Shah SM, Zimmer-Galler I, Janjua KA, Do DV, Nguyen QD. · School of Medicine, Wilmer Eye Institute, The Johns Hopkins University, Baltimore, Maryland, USA. · Ocul Immunol Inflamm. · Pubmed #18379943 No free full text.

Abstract: PURPOSE: To report an atypical case of chorioretinopathy in a patient with bilateral renal transplantations. METHODS: A 55-year-old female was referred for management of birdshot chorioretinopathy. Ophthalmologic examination revealed bilateral yellowish, chorioretinal lesions with adjacent hemorrhages. RESULTS: Angiography demonstrated lesions with hyperfluorescence, leakage, and diffuse macular edema. OCT showed intraretinal edema. Laboratory evaluation revealed IgG antibodies for Bartonella hensalae. Treatment with oral ciprofloxacin led to regression of lesions, resolution of macular edema, and improvement in visual acuity. CONCLUSION: Multifocal chorioretinal lesions associated with B. hensalae can be atypical ophthalmic manifestations of cat-scratch disease (CSD), which may occur in immunosuppressed patients. Recognition of underlying disease and appropriate therapy can lead to improved outcomes.

Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, Quinlan E, Zimmer-Galler I, Haller JA, Solomon SD, Sung JU, Hadi Y, Janjua KA, Jawed N, Choy DF, Arron JR. · Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. · Mol Ther. · Pubmed #18362932 No free full text.

Abstract: Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3 or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the 0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical coherence tomography (OCT) showed that compared to injections of 0.3 mg, injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of central retinal thickening that lasted longer between injections, but in 3 months, excess central retinal thickening which is a quantitative assessment of the macular edema, was reduced by approximately 90% in all four treatment groups. There was no correlation between the amount of improvement and duration of disease or patient age at baseline, but there was some correlation between the aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of improvement. These data indicate that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to macular edema and suggest that additional studies investigating the efficacy of intraocular injections of ranibizumab are needed.

Tatlipinar S, Shah SM, Campochiaro PA, Nguyen QD. · Retina Service, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. · Ophthalmologica. · Pubmed #17579287 No free full text.

Abstract: AIM: To assess the intraobserver repeatability of automated versus adjusted optical coherence tomography (OCT) measurements in patients with neovascular age-related macular degeneration (NVAMD). METHODS: Ten eyes with NVAMD from 10 consecutive patients underwent two OCT measurements within 5 days by a single operator. Automated and adjusted central 1-mm foveal thickness and automated and adjusted total macular volume were measured in each study eye. The term 'adjusted' refers to manually corrected values, in which the interface landmarks for measurements are selected by the operator using Stratus scan profiling and custom software. Bland-Altman method and bootstrap comparison of intraclass correlations (ICCs) were used for repeatability analysis. RESULTS: Bland-Altman comparison did not reveal any statistically significant difference in any parameter, when results at first and second examination were compared (p > 0.05), indicating that the repeated measurements are similar. Further analysis was conducted using the bootstrap comparison of ICCs. The difference between adjusted and automated foveal thickness ICCs (r = 0.945 and 0.635, respectively) was significant (p = 0.031), indicating higher repeatability for adjusted foveal thickness. The ICCs for adjusted and automated total macular volume (r = 0.873 and 0.863, respectively) showed no statistically significant difference (p = 0.881). CONCLUSION: The repeatability of adjusted retinal thickness measurements, in which the errors of retinal boundary detection by OCT analysis software is corrected by the operator using scan profiling, is found to be higher than that of automated ones in this small group of NVAMD patients when performed by a single experienced operator.

Do DV, Cho M, Nguyen QD, Shah SM, Handa JT, Campochiaro PA, Zimmer-Galler I, Sung JU, Haller JA. · Retina Division, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. · Retina. · Pubmed #17558315 No free full text.

Abstract: PURPOSE: To compare retina surgeons' recommendations for management of epiretinal membranes (ERM) and vitreomacular traction (VMT) based on clinical assessment alone with management based on clinical evaluation supplemented by optical coherence tomography (OCT). METHODS: A prospective, masked clinical case series was conducted. Surgeons first performed a complete history and physical examination on patients referred with the macular disorders under study without the benefit of adjunctive OCT, determined whether ERM, VMT, and/or macular edema were present, questionably present, or absent, and made a provisional management recommendation. The retina specialists then reviewed the OCT images for the presence or absence of ERM, VMT, and/or associated macular edema and reconsidered the final management recommendation in light of clinical evaluation combined with OCT findings. RESULTS: Eighty-four eyes of 73 patients were examined. ERM was identified in 66 (78.6%) of 84 eyes using clinical examination compared with 72 (85.7%) of 84 eyes using OCT (P = 0.06). VMT was identified in 5 (6%) of 84 eyes using clinical examination compared with 18 (21.4%) of 84 eyes using OCT (P < 0.005). Macular edema was identified in 57 (67.9%) of 84 eyes using clinical examination compared with 70 (83.3%) of 84 eyes using OCT (P = 0.003). Surgical intervention was recommended in 33 cases: 19 (57.6%) based on the history and clinical examination findings without OCT information and an additional 14 (42.4%) based on the combination of clinical evaluation and OCT findings. CONCLUSIONS: OCT is more sensitive than clinical examination in detecting ERM, VMT, and associated macular edema. Taken together with careful clinical evaluation, OCT findings influenced surgeons to recommend consideration of surgery to an additional 14 patients (42.2%) in this series.

Do DV, Cho M, Nguyen QD, Shah SM, Handa JT, Campochiaro PA, Zimmer-Galler I, Sung JU, Haller JA. · Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Trans Am Ophthalmol Soc. · Pubmed #17471336 links to  free full text

Abstract: PURPOSE: To compare retinal surgeons' recommendations for management of epiretinal membranes (ERM) and vitreomacular traction syndrome (VMT) based on clinical examination alone, with management based on examination supplemented by optical coherence tomography (OCT). METHODS: A prospective, masked clinical case series was conducted. Surgeons first assessed, on the basis of clinical examination only, whether ERM, VMT, or macular edema was present, questionably present, or absent and made a provisional management recommendation. The retina specialist then reviewed the OCT images, determined the presence or absence of ERM, VMT, or associated macular edema, and made a final management recommendation. RESULTS: Eighty-four eyes of 73 patients were examined. ERM was identified in 66 (78.6%) of 84 using clinical examination compared to 72 (85.7%) of 84 using OCT (P = .06). VMT was identified in five (6%) of 84 using clinical examination compared to 18 (21.4%) of 84 using OCT (P < .005). Macular edema was identified in 57 (67.9%) of 84 using clinical examination compared to 70 (83.3%) of 84 using OCT (P =.003). Surgical intervention was recommended in 33 cases: 19 (57.6%) based on clinical examination alone and 14 (42.4%) based on the combination of clinical examination and OCT findings. CONCLUSIONS: OCT is more sensitive than clinical examination in detecting ERM, VMT, and associated macular edema. OCT influenced the recommendation for surgical intervention in 42.4% of patients scheduled for surgery.

Anonymous00052, Browning DJ, Glassman AR, Aiello LP, Beck RW, Brown DM, Fong DS, Bressler NM, Danis RP, Kinyoun JL, Nguyen QD, Bhavsar AR, Gottlieb J, Pieramici DJ, Rauser ME, Apte RS, Lim JI, Miskala PH. · Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. · Ophthalmology. · Pubmed #17123615 links to  free full text

Abstract: OBJECTIVE: To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: Two hundred ten patients (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques. METHODS: Retinal thickness was measured with OCT and visual acuity was measured with the electronic Early Treatment of Diabetic Retinopathy procedure. MAIN OUTCOME MEASURES: Optical coherence tomography-measured center point thickness and visual acuity. RESULTS: The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months after laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% confidence interval, 3.5-5.3) of better of visual acuity for every 100-mum decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44, with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7%-17% at the 3 time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%-26% at the 3 time points). CONCLUSIONS: There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity after focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema. Thus, although OCT measurements of retinal thickness represent an important tool in clinical evaluation, they cannot substitute reliably as a surrogate for visual acuity at a given point in time. This study does not address whether short-term changes on OCT are predictive of long-term effects on visual acuity.

Do DV, Shah SM, Sung JU, Haller JA, Nguyen QD. · Vitreoretinal Service, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Am J Ophthalmol. · Pubmed #15808156 No free full text.

Abstract: PURPOSE: To assess the correlation between persistent diabetic macular edema and hemoglobin A1c (HbA1C). DESIGN: Retrospective study. METHODS: Records of type 2 diabetic patients who received eye care for persistent clinically significant macular edema (CSME) from January 2002 to January 2004 were reviewed. Subjects who met one of two criteria were identified: 1) persistent CSME, detected by contact lens biomicroscopy and fluorescein angiography, despite at least two focal laser photocoagulations (FLP) performed at least 3 months before the current diagnosis, or 2) a history of CSME with resolution of macular edema at the time of examination. Patients also needed to have had their HbA1C measured at the Johns Hopkins Hospitals within 3 months of meeting these criteria. RESULTS: The study identified 92 patients (152) eyes with persistent CSME and 32 patients (56 eyes) with resolved CSME. HbA1C values ranged from 5.3% to 15.6% (mean, 8.9%; median, 8.7%) and 5.3% to 9.7% (mean, 6.7%; median, 6.6%) among patients with persistent and resolved edema (P = .0005). Among the 32 patients with persistent unilateral CSME, mean HbA1C was 8.6% (median 8.5%), and among the 60 patients with bilateral CSME, mean HbA1C was 9.1% (median, 8.9%). Of patients with persistent CSME, 74% had HbA1C greater than 7.5% compared with 12.5% of the patients with resolved CSME (P = .0005). CONCLUSIONS: Persons with type 2 diabetes and persistent CSME have higher HbA1C at time of their disease than patients with resolved CSME. Patients with bilateral disease have more elevated HbA1C than those with unilateral disease.