Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study.

OBJECTIVES: To determine the long-term effects of ranibizumab (RBZ) in patients with diabetic macular edema (DME). DESIGN: Prospective, randomized, interventional, multicenter clinical trial. PARTICIPANTS: One hundred twenty-six patients with DME. METHODS: Subjects were randomized 1:1:1 to receive 0.5 mg RBZ at baseline and months 1, 3, and 5 (group 1), focal or grid laser photocoagulation at baseline and month 3 if needed (group 2), or a combination of 0.5 mg RBZ and focal or grid laser at baseline and month 3 (group 3). Starting at month 6, if retreatment criteria were met, all subjects could be treated with RBZ. MAIN OUTCOME MEASURES: The mean change from baseline in best-corrected visual acuity (BCVA) at month 24. RESULTS: After the primary end point at month 6, most patients in all groups were treated only with RBZ, and the mean number of injections was 5.3, 4.4, and 2.9 during the 18-month follow-up period in groups 1, 2, and 3, respectively. For the 33 patients in group 1, 34 patients in group 2, and 34 patients in group 3 who remained in the study through 24 months, the mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6-month primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24, and the percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. The percentage of patients with 20/40 or better Snellen equivalent at month 24 was 45% in group 1, 44% in group 2, and 35% in group 3. Mean foveal thickness (FTH), defined as center subfield thickness, at month 24 was 340 µm, 286 µm, and 258 µm for groups 1, 2, and 3, respectively, and the percentage of patients with center subfield thickness of 250 µm or less was 36%, 47%, and 68%, respectively. CONCLUSIONS: Intraocular injections of RBZ provided benefit for patients with DME for at least 2 years, and when combined with focal or grid laser treatments, the amount of residual edema was reduced, as were the frequency of injections needed to control edema. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Lamina puncture for central retinal vein occlusion: results of a pilot trial.

OBJECTIVE: To evaluate the effect of treatment by lamina puncture, a novel procedure to create a perivascular opening within the optic nerve head by a transvitreal approach, on visual acuity after central retinal vein occlusion (CRVO) in older patients. METHODS: The patients comprised a nonrandomized, consecutive, interventional case series of older patients being seen with CRVO. Patients 65 years or older with CRVO and a visual acuity of 20/200 or worse were treated with vitrectomy and lamina puncture of the optic disc. Preoperative visual acuity, clinical examination results, and fluorescein angiography results were compared with postoperative results. RESULTS: Twenty patients (12 men and 8 women), an average age of 72 years, were enrolled. The mean duration of CRVO was 5.4 months; 14 eyes had nonischemic CRVO when first seen, while 6 had substantial ischemia. The mean preoperative visual acuity was in the counting fingers range, and the mean postoperative visual acuity was also in the counting fingers range. Complications included 5 eyes with iris neovascularization, of which 4 progressed to neovascular glaucoma; also, preoperative ischemia seemed to predispose to neovascular complications. CONCLUSION: Lamina puncture does not restore visual acuity in older patients with CRVO.

Retinal microvascular surgery: a feasibility study.

PURPOSE: To evaluate the feasibility of microvascular surgery at the level of the retinal vasculature. METHOD: Porcine eyes were used, and eyecups were prepared under an operating microscope. Several classic microvascular maneuvers were explored, such as vascular puncturing, catheterization, mobilization, intravascular injections, and various combinations of the same. Instruments used ranged from disposable 30-gauge needles to an Er:YAG laser. Commercially available 10-0 nylon sutures, fine polyimide tubes, and custom-made fine glass tubes were used for vascular catheterization. RESULTS: Puncturing, mobilization, catheterization, and intravascular injection of retinal arteries and veins were possible. The connection of two remote retinal vessels with a fine tube was also achieved with the combination of these maneuvers. CONCLUSIONS: The feasibility of performing several microvascular maneuvers on retinal arteries and veins was demonstrated in porcine eyes. Further experimentation and development of these findings in a living animal model could lead to the development of such microvascular maneuvers in humans.

In vivo rabbit eyecup preparation for use in retinal research.

PURPOSE: To develop an in vivo rabbit eyecup preparation that preserves neuronal and vascular connections with normal posterior segment contour, permitting direct access to the retina and facilitating retinal microsurgical and neuroscience research. METHODS: Cyanoacrylate glue was applied to the anterior sclera of six Dutch-belted rabbits before open-sky vitrectomy. The glue was used to harden the compliant scleral wall and to fix it to the surrounding periorbital tissues. RESULTS: A normal contour of the posterior segment was retained in all cases. Vitrectomy under air was successfully accomplished and an extensive removal of the vitreous gel was achieved. Fluorescein angiography revealed normal vascular patency of the retinal vessels after vitrectomy. CONCLUSIONS: The proposed modification of the rabbit eyecup retains the normal neurovascular connections and configuration of the retina, making it suitable for retinal microsurgical maneuvers or any procedures in which easy access to anatomically undisturbed retina is required.

Lamina puncture: pars plana optic disc surgery for central retinal vein occlusion.

OBJECTIVE: To determine the feasibility of creating a perivascular space adjacent to the central retinal vein at the level of the lamina cribrosa as a potential method of reestablishing perfusion in central retinal vein occlusion. METHODS: Various designs for a puncture instrument, or lamina puncture lancet, were investigated in cadavers, pigs that had undergone enucleation, and in vivo rabbit eyes. RESULTS: A lancet with a sharp cutting edge on one side and an opposing blunt edge is repeatedly able to create a perivascular space with limited optic nerve fiber damage. CONCLUSIONS: Lamina puncture is technically feasible, and evaluation in carefully selected patients appears warranted.

Topical mecamylamine for diabetic macular edema.

PURPOSE: Stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. The safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, was tested in patients with diabetic macular edema. DESIGN: A multicenter phase I/II clinical trial. METHODS: Twenty-three patients with chronic diabetic macular edema received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA), and measurement of foveal thickness using optical coherence tomography at baseline, 1, 4, 8, 12, and 16 weeks. RESULTS: Mecamylamine drops were well tolerated and there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12, and 16 weeks was 2.8, 1.9, 2.4, 0.8, and 3.1 letters, respectively. There was little change in mean excess foveal thickness. There was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness, or both, 9 patients showed equivocal or no substantial changes, and 4 patients showed worsening. Five patients showed a substantial improvement in BCVA, foveal thickness, or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine. CONCLUSIONS: This study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with diabetic macular edema. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects.