Papers by Magdalena Krzystolik
Reviews, 1996
Antiangiogenic therapy is a new approach to the treatment of neovascular age-related macular dege... more Antiangiogenic therapy is a new approach to the treatment of neovascular age-related macular degeneration. Interferon alfa is one antiangiogenic agent thought to function by inhibiting the migration and proliferation of vascular endothelial cells. It has been used in the treatment of hepatitis, solid tumors and hematologic malignancies. The aim of this review was to investigate interferon alfa as a treatment modality for neovascular age-related macular degeneration. We searched and identified trials from the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Group Trials Register, in The Cochrane Library (Issue 2, 2005), MEDLINE (1966 to 2005/06 week 1), EMBASE (1980 to 2005/week 23), LILACS (Latin American and Caribbean Health Science Literature Database) (June 2005) and the reference lists of included studies. This review included randomized controlled trials evaluating interferon alfa therapy in people with neovascular age-related macular degeneration who were followed for at least one year. Both review authors independently extracted data and assessed trial quality. No data synthesis was conducted as only one trial met the inclusion criteria. The one included trial enrolled and randomized 481 participants from 45 centers worldwide into four groups. The study allowed for analysis of the number of participants who had lost three or more lines of vision at 52 weeks in three interferon alfa-2a groups versus placebo. The results show an odds ratio of 1.60 (95% Confidence Interval 1.01 to 2.53) indicating that interferon is associated with a 60% increased odds of losing three or more lines at 52 weeks. This finding is marginally statistical with a P value of 0.04 and indicates that the treatment has the potential for harm rather than benefit. At present there is not enough evidence to recommend the use of interferon alfa-2a for the treatment of age-related macular degeneration.
Ophthalmology, Jan 15, 2015
To summarize the relative effects of bevacizumab (Avastin; Genentech, Inc, South San Francisco, C... more To summarize the relative effects of bevacizumab (Avastin; Genentech, Inc, South San Francisco, CA) and ranibizumab (Lucentis; Genentech, Inc.), using findings from a Cochrane Eyes and Vision Group systematic review. Neovascular age-related macular degeneration (NVAMD) is the most common cause of uncorrectable vision loss among the elderly in developed countries. Bevacizumab and ranibizumab are the most frequently used anti-vascular endothelial growth factor (VEGF) agents injected intravitreally to treat NVAMD. For this systematic review, we included only randomized controlled trials in which the 2 anti-VEGF agents had been compared directly. The primary outcome was 1-year gain in best-corrected visual acuity (BCVA) of ≥15 letters. We followed Cochrane methods for trial selection, data extraction, and data analyses. Relative effects of bevacizumab versus ranibizumab are presented as estimated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We identi...
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, Jan 15, 2015
Reviews, 1996
Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the form... more Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG. To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013. We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken. No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the study participants. Currently available evidence is insufficient to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering IOP in NVG. Well designed RCTs are needed to address this issue, particularly trials that evaluate long-term (at least six months) benefits and risks since the effects of anti-VEGF agents may be short-term only. An RCT comparing anti-VEGF agents with no anti-VEGF agents taking into account the need for co-interventions, such as panretinal photocoagulation (PRP), glaucoma shunt procedures, cyclodestructive procedures, cataract surgery, and deep vitrectomy, could be of use to investigate the additional beneficial effect of anti-VEGF agents in treating NVG. Since decisions for when and which co-interventions should be used are based on clinical criteria, they would not be appropriate for randomization. However, the design of a study on this topic should aim to balance groups by stratification of co-intervention at time of randomization or by enrolling a sufficient number of participants to conduct subgroup analysis by co-interventions (ideally 15 participants per treatment group for each subgroup). Alternatively, the inclusion criteria for a trial could limit participants to those who receive the same co-intervention.
Ophthalmology, 2007
Purpose-To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic ... more Purpose-To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME).
Neuron, 2000
In the mouse, the classic work of Carter- LaVail (1979a, 1979b) best documents the rod and cone c... more In the mouse, the classic work of Carter- LaVail (1979a, 1979b) best documents the rod and cone cell types. The retina is rod dominated. Cones constitute only 3% of the photoreceptors and are evenly spaced across the retina. While the cell morphology distinguishes cones from rods, it does not reveal different cone cell Boston, Massachusetts 02114 types. At the time of the Carter-Dawson and LaVail work (1979a, 1979b), there were no good markers for cone subtypes. Szé l, Rö hlich, and colleagues initiated studies of cone subtypes in the murine retina and explored their Summary topography (Szé l and Rö hlich, 1992; Szé l et al., 1992, 1994). Their work with the C57BL mouse, using mono-Mice express S and M opsins that form visual pigments clonal antibodies to chicken opsins, suggested that S for the detection of light and visual signaling in cones. cones were primarily in the ventral retina and M cones Here, we show that S opsin transcription is higher were only in the dorsal retina, thus accounting for the even than that of M opsin, which supports ultraviolet (UV) distribution of cone number across the retina. Additional sensitivity greater than midwavelength sensitivity. studies of cone topography in different species of Mus Surprisingly, most cones coexpress both S and M opand Apodemus indicate that both S and M cones can vary sins in a common cone cell type throughout the retina. in pattern; depending upon the species, patterns exhibit All cones express M opsin, but the levels are graded uniform, gradient, or no expression of S or M opsin (Szé l from dorsal to ventral. The levels of S opsin are relaet al., 1994). Mechanisms by which patterns might vary tively constant. However, in the far dorsal retina, S among genera have not been considered. opsin is repressed stochastically, such that some Rod and cone photoreceptors are generally considered cones express M opsin only. These observations indito express a single opsin, which covalently binds 11-cis cate that two different mechanisms control M and S retinaldehyde to produce a visual pigment with a unique opsin expression. We suggest that a common cone absorption spectrum. While the S and M cones are considtype is patterned across the retinal surface to produce ered to be the two cone types in the mouse, several studies phenotypic cone subtypes. challenge the strict interpretation that they are exclusive cell types. A lacZ reporter driven by a human upstream M cone control region is not restricted to M cones but is Introduction expressed in both cone types (Wang et al., 1992). Likewise, the full human L opsin gene (Shaaban et al., 1998) and Rod and cone photoreceptor cells of the retina enable the reporter transgenes for the full human X chromosome detection of light and initiation of visual signaling. The tandem L/M gene array (Wang et al., 1999) are expressed spectral range of detection is controlled by the selected in both cone types in transgenic animals. Moreover, the expression of visual pigments differing in absorption specmouse is one of a growing list of animals in which some tra. The threshold and amplitude of response to light are form of dual expression of opsins in a common photoreinfluenced by the levels of pigment expression within these ceptor type is documented. Rö lich and colleagues (1994) cells. In addition, the retinal topography, or retinal mosaic, indicate that S and M opsins are coexpressed in one of photoreceptors contributes the potential for color vicone type in a narrow horizontal "transition zone" near sion, spatial resolution, and orientation of visual scenes the horizontal midplane of the retina. Physiological studies (Rodieck, 1998). These attributes vary widely from animal of mouse electroretinograph (ERG) signals confirm that to animal. Evolutionary adaptation to differing environsome proportion of cones express both S and M opsins ments has affected the selection of pigment isoforms, the (Lyubarsky et al., 1999). These observations call for clarifilevel of pigment expression, the number of photoreceptor cation of the nature of the cone types and their topographicell types, and the spatial organization of photoreceptors (Jacobs, 1993). cal organization, since these parameters affect our considerations for mechanisms of cell differentiation, control of opsin expression, and properties of color vision. . 4% paraformaldehyde in 0.1 M MOPS (pH 7.4), 2 mM EGTA, and 1 mM MgS0 4 and then cut along the ora serrata to remove the cornea and lens. After marking the dorsal orientation by incision, retinae References were teased out gently and refixed in a microfuge tube for 03ف min. Solution hybridization was carried out on the retinae using a protocol Al-Ubaidi, M.R., Pittler, S.J., Champagne, M.S., Triantafyllos, J.T., adapted from Harland (1991), Conlon and Herrmann (1993), and McGinnis, J.F., and Baehr, W. (1990). Mouse opsin. Gene structure Wilkinson (1992). Digoxigenin dUTP-labeled sense and antisense and molecular basis of multiple transcripts. J. Biol. Chem. 265, riboprobes (Figures 1A-1C) were prepared, hybridized, and devel-20563-20569. oped using the Genius System. Small cuts were made in the retinae Archer, S.N., and Lythgoe, J.N. (1990). The visual pigment basis for to facilitate flat mounting on silylated slides (Onasco Products, cone polymorphism in the guppy, Poecilia reticulata. Vision Res. Houston, TX), photoreceptor side up. 30, 225-233.
Journal of the American Geriatrics Society, 2013
Archives of Ophthalmology, 2002
Objective: To evaluate the safety and efficacy of intravitreal injections of an antigen-binding f... more Objective: To evaluate the safety and efficacy of intravitreal injections of an antigen-binding fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV).
American Journal of Ophthalmology, 1998
PURPOSE: To illustrate succinctly the various stages of macular hole formation. METHOD: We photod... more PURPOSE: To illustrate succinctly the various stages of macular hole formation. METHOD: We photodocumented the evolution of a full-thickness macular hole in a patient who refused surgery. RESULTS: A 60dyeareold woman, who had had difficulty reading for 3 months, was initially examined with a stage 1B macular hole in her right eye that progressed to stage 2 over a 6-month period and then to stage 3, 2 years after initial examination.
American Journal of Ophthalmology, 2012
Archives of Ophthalmology, 2006
To determine predictors of choroidal neovascularization (CNV) and visual outcome after traumatic ... more To determine predictors of choroidal neovascularization (CNV) and visual outcome after traumatic choroidal rupture. A retrospective review of patients with traumatic choroidal rupture diagnosed in the Retina Service, Massachusetts Eye and Ear Infirmary, Boston, between January 1993 and August 2001 was performed. Parametric and nonparametric statistical methods were used to evaluate visual prognosis, CNV, and retinal detachment after traumatic choroidal rupture. One hundred eleven cases were identified and reviewed. Visual acuity (VA) changes were recorded in all of the cases. Thirty-eight (34%) of the 111 patients recovered driving vision (VA > or =20/40). Rupture location was recorded in 107 cases. Recovery of driving vision was seen in 20 (59%) of 34 eyes with peripheral choroidal ruptures, 17 (22%) of 73 eyes with macular choroidal ruptures, 38 (38%) of 99 eyes without CNV, 1 (8%) of 12 eyes with CNV, 38 (40%) of 96 eyes without retinal detachment, and 1 (7%) of 15 eyes with retinal detachment. Older age and location of rupture within the arcades were positively associated with CNV formation (P = .04 and .03, respectively). Foveal location of rupture, multiple ruptures, and poor baseline VA were associated with failure to recover driving vision in univariate regression analyses. In multivariate analysis, rupture location and baseline VA were independently associated with visual outcome. Of 12 patients diagnosed with CNV, 5 were not treated, 4 were treated with argon laser photocoagulation, 1 was treated with surgery, 1 was treated with argon laser photocoagulation followed by surgery, and 1 was treated with verteporfin photodynamic therapy. Most patients with traumatic choroidal rupture do not achieve final VA of 20/40 or better. Poor visual outcome was most highly associated with a macular rupture and baseline VA of less than 20/40. The formation of CNV was most strongly associated with older age and macular choroidal rupture.
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Papers by Magdalena Krzystolik