Macular Degeneration: Do DV

Kaiser PK, Do DV. · Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. · Int J Clin Pract. · Pubmed #17313620 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of adult blindness among individuals aged 50 and older in the Western world, with the neovascular form of AMD responsible for the most severe and rapid visual loss. Although monotherapy with currently available treatments can slow the rate of loss of vision in eyes with neovascular AMD, they do not significantly improve vision. Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment that targets all VEGF-A isoforms and their biologically active degradation products. Clinical trials have reported that ranibizumab treatment resulted in greater proportions of patients achieving a < 15 letter loss of visual acuity and improved vision at 12 and 24 months than control groups. The incidence of serious ocular and systemic adverse events was low in all ranibizumab trials to date. Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate significant improvement in vision for many patients and represents a major advance in treating neovascular AMD.

Virgili G, Do DV, Bressler NM, Menchini U. · Department of Oto-Neuro-Ophthalmological Surgical Sciences, University of Florence, Florence, Italy. · Acta Ophthalmol Scand. · Pubmed #17244204 No free full text.

Abstract: During the past 20 years, several multicentre clinical trials have investigated different therapies for neovascular age-related macular degeneration (AMD). These landmark studies have provided the scientific community with powerful data regarding the ability of laser photocoagulation, verteporfin therapy, pegaptanib sodium and submacular surgery to treat particular choroidal neovascular lesion types. Accurate interpretation of data from these trials is essential to enable clinicians to make informed decisions about therapeutic interventions. Furthermore, several new treatment options are likely to become available in the next few years and clinicians will have to decide how effective these therapies may be, and how (or if) they should be used in clinical practice. It is therefore timely to review the strengths and weaknesses of the body of evidence for the currently available therapeutic options for patients with choroidal neovascularization due to AMD. Evaluation of the quality of reporting in past clinical trials will also enable critical review of new studies that will be published in the future. This review summarizes the design, reporting and results of key randomized clinical trials, in addition to evaluating the available evidence for new therapies and identifying the important issues that need to be considered when evaluating their efficacy.

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.

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.

Sabet-Peyman EJ, Heussen FM, Thorne JE, Casparis H, Patel SJ, Do DV. · Retina Division, The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Ophthalmic Surg Lasers Imaging. · Pubmed #19485300 No free full text.

Abstract: A 37-year-old woman with bilateral obliterative retinal vasculitis and macular ischemia received intravitreal bevacizumab for rapidly progressive neovascularization of the optic disc and vitreous hemorrhage in the left eye. One week after treatment, she presented with central scotoma and fluorescein angiography revealed increased parafoveal capillary dropout and progressive macular ischemia in the treated eye.

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.

Nguyen-Khoa BA, Goehring EL, Werther W, Gower EW, Do DV, Jones JK. · The Degge Group, Ltd, Arlington, Virginia, USA. · Arch Ophthalmol. · Pubmed #18779491 No free full text.

Abstract: OBJECTIVE: To compare the incidence rate of hospitalized myocardial infarctions (MIs) and cerebrovascular accidents (CVAs) in subjects with and without neovascular age-related macular degeneration (AMD). METHODS: A retrospective database cohort study was performed in subjects with neovascular AMD and controls matched for age, sex, geography, and enrollment duration. Healthcare claims for the study period from January 1, 2002, to June 30, 2005, were used to identify subjects and outcomes. Incidence of hospitalized MI and CVA events and rate ratios adjusted for 11 risk factors were calculated. RESULTS: In 7203 subjects with neovascular AMD and 20,208 controls, the rate of MI was 16.2 events per 1000 subjects with neovascular AMD and 23.1 events per 1000 controls. The adjusted rate ratio for MI was 0.58 (95% confidence interval, 0.48-0.72; P < .001) for subjects with neovascular AMD vs controls. The rate of CVA was 14.3 events per 1000 subjects with neovascular AMD and 22.1 events per 1000 controls. The adjusted rate ratio for CVA was 0.56 (95% confidence interval, 0.45-0.70; P < .001). CONCLUSIONS: Rates of MI or CVA were significantly lower in subjects with neovascular AMD than in controls. These findings could not be explained by systematic differences in case selection, health care use, or comorbidities, although other possible biases cannot be ruled out.

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.

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.

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.

Do DV, Bressler NM, Bressler SB. · The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. · Am J Ophthalmol. · Pubmed #15013883 No free full text.

Abstract: PURPOSE: To report the occurrence of large submacular hemorrhages after photodynamic therapy with verteporfin in age-related macular degeneration patients with subfoveal choroidal neovascularization (CNV) composed of occult with no classic CNV in whom the hemorrhage precluded determining if additional therapy should be given within 3 months after initiation of treatment. DESIGN: Retrospective, noncomparative case series. METHODS: The records of all age-related macular degeneration patients who received verteporfin therapy for subfoveal lesions composed of occult with no classic CNV between February and July 2001 at The Wilmer Eye Institute were reviewed. Subjects who reported either having undergone a procedure to remove intraocular blood before a month 3 follow-up visit, or who had submacular hemorrhage at the month 3 visit that was severe enough to preclude determining if additional verteporfin therapy should be given were identified. RESULTS: Fifty-five eyes of 52 patients were reviewed. Five eyes (9% [95% confidence interval, 1.4%-16.6%]) developed submacular hemorrhage that precluded determining if additional verteporfin therapy should be given. Visual acuity 3 months after documentation of the hemorrhage decreased a median of 8.5 lines compared with pretreatment acuity. CONCLUSIONS: Even in the absence of acute severe visual acuity decrease, submacular hemorrhage after verteporfin therapy can be associated with severe vision loss and preclude determining if additional therapy should be given.