Macular Degeneration: Shah SM

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.

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.

Ghazi NG, Ciralsky JB, Shah SM, Campochiaro PA, Haller JA. · Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA. · Am J Ophthalmol. · Pubmed #17869207 No free full text.

Abstract: PURPOSE: To assess the optical coherence tomography (OCT) characteristics of eyes with persistent clinically significant diabetic macular edema (PDME) after focal laser treatment, with emphasis on the vitreomacular interface (VMI) characteristics. DESIGN: Prospective, observational case series. METHODS: Fifty eyes with PDME after at least one focal laser treatment were enrolled prospectively. Slit-lamp biomicroscopy, stereoscopic fundus photography, fluorescein angiography (FA), and OCT were performed for each eye. The main outcome measures included the detection rate of VMI abnormalities (VMIA) by OCT in comparison with biomicroscopy, fundus photography, and FA (traditional techniques); the relationship between VMIA and the number of focal laser sessions per eye and FA leakage pattern. RESULTS: Two of 50 eyes were excluded because of incomplete data. For the remaining 48 eyes, 25 eyes (52.1%) demonstrated definite VMIA, including anomalous vitreal adhesions, epiretinal membrane (ERM), or both, and six eyes (12.5%) had questionable VMIA. OCT in general was 1.94 times more sensitive than traditional techniques combined in detecting VMIA (P = .00003). The number of focal laser sessions and diffuse FA leakage were not associated with an increased prevalence of VMIA (P = .13 and P = .47, respectively). CONCLUSIONS: This study demonstrates a high prevalence of VMIA in eyes with PDME after focal laser treatment and underscores the superiority of OCT in detecting these abnormalities. OCT evaluation of eyes with PDME may be helpful in identifying VMIA, which may impact treatment selection and patient subgroup stratification.

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.

Mac Gabhann F, Demetriades AM, Deering T, Packer JD, Shah SM, Duh E, Campochiaro PA, Popel AS. · Department of Biomedical Engineering, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 720 Rutland Ave, #613 Traylor, Baltimore, MD 21205, USA. · Ann Biomed Eng. · Pubmed #17277991 No free full text.

Abstract: Ocular neovascularization is a major cause of blindness in several diseases including age-related macular degeneration (choroidal neovascularization) and diabetic retinopathy (retinal neovascularization). Antiangiogenic agents with clinically significant effects exist, but a key question remains: how to effectively deliver drugs to the site of neovascularization. Periocular delivery of drugs or proteins is less invasive and safer than intravitreous delivery, but little is known regarding how and to what extent agents access intraocular tissues after periocular injection. We present a computational model of drug or protein transport into the eye following periocular injection to quantify movement of macromolecules across the sclera of the mouse eye. We apply this model to the movement of green fluorescent protein (GFP) across the mouse eye and fit the results of in vivo experiments to find transport parameters. Using these parameters, the model gives the profile of interstitial GFP concentration across the sclera, choroid and retina. We compare this to predictions of transport following intravitreous injections. We then scale up the model to estimate the transport of GFP into the human choroid and retina; the thicker sclera decreases transscleral delivery. This is the first model of ocular drug delivery to explicitly account for transport properties of each eye layer.

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.

Raina J, Bainbridge JW, Shah SM. · St Bartholomew's Hospital, London, UK. · Eye. · Pubmed #10755092 No free full text.

Abstract: PURPOSE: To investigate the causes of decreased visual acuity in patients with cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS). METHODS: All human immunodeficiency virus (HIV)-positive patients seen in two ophthalmology units over a 15 month period from September 1996 were included in this retrospective study. A detailed ophthalmic examination was performed on all patients and in addition those with CMV retinitis underwent serial fundus photography. Decreased visual acuity was defined as a best corrected visual acuity < or = 6/12. CMV and retroviral treatment, CD4+ count and HIV viral load were also documented for each patient. RESULTS: Of 110 patients seen over the 15 month period, 26 (41 eyes) had a diagnosis of CMV retinitis. Twelve patients (16 eyes) with CMV retinitis had decreased visual acuity. The decreased visual acuity in 7 eyes was initially due to the CMV retinitis involving the macula and the optic nerve. Retinal detachment was responsible in 2 eyes and optic nerve atrophy in 1 eye. In 6 eyes (4 patients) the decreased visual acuity was due to a maculopathy--cystoid macular oedema and/or an epiretinal membrane in the presence of an inactive zone 2 or 3 CMV retinitis--with all these patients exhibiting a vitritis of varying grade. The decreased visual acuity in the maculopathy subgroup was irreversible in all except 1 eye, and 2 eyes in this category later developed a cataract. CONCLUSION: In this series, CMV-retinitis-'related' maculopathy was a major (38%) cause of decreased visual acuity, occurring in the absence of zone 1 retinitis and despite inactive peripheral CMV retinitis. A varying degree of vitritis was an associated feature in all these patients. This study therefore highlights maculopathy as an important and previously unrecognised significant cause of visual morbidity in CMV retinitis.