Macular Degeneration: Ezra E

Zambarakji HJ, Lane AM, Ezra E, Gauthier D, Goitein M, Adams JA, Munzenrider JE, Miller JW, Gragoudas ES. · Retina Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA. · Ophthalmology. · Pubmed #16935343 No free full text.

Abstract: OBJECTIVE: To evaluate safety and visual outcomes after proton therapy for subfoveal neovascular age-related macular degeneration (AMD). DESIGN: Randomized dose-ranging clinical trial. PARTICIPANTS: One hundred sixty-six patients with angiographic evidence of classic choroidal neovascularization resulting from AMD and best-corrected visual acuity of 20/320 or better. METHODS: Patients were assigned randomly (1:1) to receive 16-cobalt gray equivalent (CGE) or 24-CGE proton radiation in 2 equal fractions. Visual acuity was measured using standardized protocol refraction. Complete ophthalmological examinations, color fundus photography, and fluorescein angiography were performed before and 3, 6, 12, 18, and 24 months after treatment. MAIN OUTCOME MEASURE: Proportion of eyes losing 3 or more lines of vision from baseline. Kaplan-Meier statistics were used to compare cumulative rates of vision loss between the 2 treatment groups. RESULTS: At 12 months after treatment, 36 eyes (42%) and 27 eyes (35%) lost 3 or more lines of vision in the 16-CGE and 24-CGE groups, respectively. Rates increased to 62% in the 16-CGE group and 53% in the 24-CGE group by 24 months after treatment (P = 0.40). Radiation complications developed in 15.7% of patients receiving 16 CGE and 14.8% of patients receiving 24 CGE. CONCLUSIONS: No significant differences in rates of visual loss were found between the 2 dose groups. Proton radiation may be useful as an adjuvant therapy or as an alternative for patients who decline or are not appropriate for approved therapies.

Husain D, Kim I, Gauthier D, Lane AM, Tsilimbaris MK, Ezra E, Connolly EJ, Michaud N, Gragoudas ES, O'Neill CA, Beyer JC, Miller JW. · Angiogenesis and Laser Laboratory, Retina Service, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA. · Arch Ophthalmol. · Pubmed #15824225 No free full text.

Abstract: OBJECTIVE: To study the safety and efficacy of intravitreal injections of anti-vascular endothelial growth factor antibody fragment (ranibizumab [formerly known as rhuFabV2], Lucentis; Genentech, South San Francisco, Calif) in combination with intravenous verteporfin (Visudyne; Novartis, East Hanover, NJ) photodynamic therapy (PDT) on experimental choroidal neovascularization in the monkey eye. METHODS: Choroidal neovascularization was induced by laser injury in both eyes of cynomolgus monkeys and followed with weekly fundus photography and fluorescein angiography. Two weeks after induction, weekly treatments were initiated. These treatments included using either an intravitreal injection of ranibizumab (previously known as rhuFabV2) in combination with verteporfin PDT or a ranibizumab vehicle (placebo) in combination with verteporfin PDT (PDT only). Six animals (group 1) initially received intravitreal injections followed 1 week later by PDT. Four animals (group 2) initially received PDT followed 1 week later by intravitreal injection. Two animals (group 3) received injections and PDT on the same day at 2-week intervals. Photodynamic therapy was applied in all 3 groups every 2 weeks for 3 treatments with follow-up through 2 weeks after the last PDT treatment. Fluorescein angiograms were graded using a masked standardized protocol. The data were analyzed using the McNemar chi(2) test for matched pairs. RESULTS: No choroidal neovascularization leakage was observed in the eyes of animals treated with ranibizumab and PDT at day 21 or 42 after the start of the first treatment. Leakage persisted in eyes treated with PDT alone at 21 days (3 of 12 eyes) and 42 days (2 of 12 eyes). At all time points studied, the ranibizumab and PDT-treated eyes experienced better angiographic outcomes than the eyes receiving PDT alone. CONCLUSION: These preliminary data indicate that an intravitreal ranibizumab injection in combination with verteporfin PDT (ranibizumab and PDT) causes a greater reduction in angiographic leakage than PDT and intravitreal vehicle injection (PDT only) in experimental choroidal neovascularization. CLINICAL RELEVANCE: This combination therapy can potentially offer a new treatment modality for choroidal neovascularization in patients with macular degeneration and other diseases.

Knupp C, Munro PM, Luther PK, Ezra E, Squire JM. · Biological Structure and Function Section, Biomedical Sciences Division, London, SW7 2AZ, United Kingdom. · J Struct Biol. · Pubmed #10675295 No free full text.

Abstract: Transversely banded deposits with an approximately 100-nm periodicity have been seen in association with a number of eye pathologies (e.g., age-related macular degeneration). Recently such aggregates have also been discovered in the cortical vitreous of a patient suffering from full thickness macular holes. The aggregates in the vitreous were of sufficient size and regularity for us to attempt 3D ultrastructural studies in the electron microscope. The molecules forming this aggregate pack in a centered tetragonal unit cell of dimensions approximately 26 x 26 x 180 nm. A real-space (r-weighted back projection) 3D reconstruction was computed. The aggregate is discussed in terms of its possible protein constituents. Collagen VI has been singled out as the most likely protein to form the aggregate. Two alternative models for the molecular packing are proposed, comprising aggregates of molecular tetramers or octamers. Understanding the structure of these abnormal banded deposits in the eye should help to throw light on the pathophysiological mechanisms of the diseases, including age-related macular degeneration, in which they occur.

Scott RA, Ezra E, West JF, Gregor ZJ. · Moorfields Eye Hospital, City Road, London EC1V 2PD. · Br J Ophthalmol. · Pubmed #10655189 links to  free full text

Abstract: AIMS: To determine the visual and anatomical outcome of surgery for long standing idiopathic macular holes. METHODS: A retrospective review of 24 eyes of all 22 patients who underwent surgery for idiopathic full thickness macular holes (FTMH) symptomatic for between 1 and 3 years. Postoperative follow up was for 6 months. Preoperative and postoperative visual acuities were recorded as well as the presence of anatomical closure of the hole. RESULTS: The mean duration of symptoms was 18.21 (SD 5.42) months). Anatomical closure of the FTMH was achieved in 17 (70.8%) of the eyes at 6 months. The logMAR acuity of the group where closure was achieved improved by a mean of 0.31, equivalent to a change of Snellen acuity from 6/60 to 6/29. Where the hole remained open the acuity deteriorated by a mean logMAR of 0.11 lines, equivalent to a change of Snellen acuity from 6/60 to 5/60. Anatomical closure of the hole was associated with a significantly improved acuity over non-closure (p<0.001). The degree of visual improvement was independent of the preoperative visual acuity (Spearman correlation coefficient 0.03, p=0.888), though preoperative acuity was related to the final acuity (Spearman correlation coefficient 0.701, p<0.001). Over the study period, six patients required cataract surgery, one patient developed secondary glaucoma, and one a retinal detachment. CONCLUSIONS: Vitrectomy with intraocular gas tamponade and postoperative posturing is a well tolerated and effective intervention for long standing macular holes. Anatomical closure of the macular hole is associated with a significant improvement in visual acuity.

Georgalas I, Pavesio C, Ezra E. · No affiliation provided · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17562067 No free full text.

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