Howard F. Fine

Intravitreal bevacizumab (Avastin) treatment of macular edema in central retinal vein occlusion: a short-term study.

Purpose: To report the short term anatomic and visual acuity response after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with macular edema due to central retinal vein occlusion (CRVO). Methods: The authors conducted a retrospective study of patients with macular edema due to CRVO who were treated with at least one intravitreal injection of bevacizumab 1.25 mg in 0.05 mL. Patients underwent Snellen visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination at baseline and follow-up visits. Results: There were 16 eyes of 15 consecutive patients with a mean age of 76.1 years (SD 9.8 years). Intravitreal triamcinolone had been previously administered to 9 patients, but all of these patients either had no improvement or had excessive intraocular pressure caused by the triamcinolone. The patients received a mean of 2.8 injections of bevacizumab per eye. No adverse events were observed, including endophthalmitis, clinically evident inflammation, increased intraocular pressure, retinal tears, retinal detachment, or thromboembolic events in any patient. The mean central macular thickness at baseline was 887 &mgr;m and decreased to a mean of 372 &mgr;m at month 1 (P < 0.001). The mean baseline acuity was 20/600 (logMAR = 1.48) and the mean acuity at month 1 was 20/200 (logMAR = 1.05), a difference that was highly significant (P = 0.001). At last follow-up, a mean of 3 months after the first injection, the mean visual acuity was 20/138 (logMAR = 0.84), which was significantly better than baseline (P < 0.001). Visual acuity improvement, defined as a halving of the visual angle, was seen in 14 of the 16 eyes. Conclusion: Initial treatment results of patients with macular edema secondary to CRVO did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular edema and improvement in visual acuity. The number of patients in this pilot study was limited and the follow-up is too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Intravitreal bevacizumab for the management of choroidal neovascularization in pseudoxanthoma elasticum.

Purpose: To determine the results of intravitreal bevacizumab injections for the management of choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE)–associated angioid streaks. Methods: A consecutive series of patients with PXE and CNV were managed with intravitreal bevacizumab injection (1.25 mg per 0.05 cc). The main outcome measures were visual acuity and greatest lesion height as measured by optical coherence tomography (OCT). Results: Nine eyes of nine consecutive patients received intravitreal bevacizumab (1.25 mg/0.05 mL) injections. The mean follow-up time was 6 months, during which eyes received an average of 1.8 injections. The baseline visual acuity was a mean of 20/368 and improved to 20/289 at the last visit (P = 0.056). Visual acuity either improved or stabilized in all 9 eyes (100%). Serial OCT measurements in 8 eyes showed a mean of 353 &mgr;m at baseline, which decreased to 201 &mgr;m at the last visit (P = 0.012). No complications were noted. Conclusions: These short-term results support the use of intravitreal bevacizumab for the management of CNV in patients with PXE. Continued experience with intravitreal bevacizumab in this population will help establish its longer-term efficacy and better define the potential need for serial injections to maintain these results.

BEVACIZUMAB (AVASTIN) AND RANIBIZUMAB (LUCENTIS) FOR CHOROIDAL NEOVASCULARIZATION IN MULTIFOCAL CHOROIDITIS

Background: Multifocal choroiditis (MFC) is an inflammatory condition, occasionally associated with choroidal neovascularization (CNV). Bevacizumab (Avastin) and ranibizumab (Lucentis) are therapies that target vascular endothelial growth factor. Bevacizumab and ranibizumab have been used successfully to treat CNV in age-related and myopic macular degeneration. Purpose: To describe the treatment of MFC-associated CNV with intravitreal bevacizumab and/or ranibizumab. Design: Retrospective interventional case series. Participants: Six eyes of five patients with MFC-associated CNV were treated with intravitreal bevacizumab and/or ranibizumab. Main Outcome Measures: Visual acuity at 1, 3, and 6 months after the initial injection. Results: Previous therapies (number of eyes treated) included sub-Tenons corticosteroids (2), intravitreal corticosteroids (1), photodynamic therapy (1), and thermal laser (1). The mean number (range) of antivascular endothelial growth factor injections per eye was 2.3 (1–6). The mean duration (range) of follow-up per patient was 41.5 (25–69) weeks. Five of six eyes improved to 20/30 acuity or better at 6 months. One eye suffered a subfoveal rip of the retinal pigment epithelium with 20/400 acuity. There was a qualitative decrease in clinical and angiographic evidence of CNV. Conclusions: Bevacizumab and ranibizumab were effective at improving visual acuity over 6 months in a small series of patients with MFC-associated CNV. Tears of the retinal pigment epithelium may occur after intravitreal antivascular endothelial growth factor therapy in MFC-associated CNV.

Design and Theoretical Evaluation of Micro-Surgical Manipulators for Orbital Manipulation and Intraocular Dexterity

This paper addresses the design considerations and dexterity evaluation of a novel hybrid two-armed micro-surgical slave robot equipped with intraocular dexterity devices. A unified framework for the kinematic modeling of this robot is presented while using the kinematic constraints stemming from the constrained motion of the eye. An augmented Jacobian describing the kinematics of the eye and the relative motion of each one of the two intraocular dexterity robots (IODR) is presented. Using this framework, the capabilities of this two-armed robot in performing dexterous intraocular operations are evaluated and compared to a similar robot without intraocular dexterity. The kinematic conditioning index (KCI) for the proposed robot is shown to be significant. The results presented show an increase of approximately 33% and 47% in translational and rotational KCI respectively

Performance Evaluation for Multi-arm Manipulation of Hollow Suspended Organs

This paper presents a unified mathematical framework for modeling and evaluating the performance of multiple robotic arms that operate on hollow suspended organs. This framework is applied to a novel two-armed hybrid robotic system being developed for ophthalmic vitreous surgeries. Four cases are designated to capture the general movements required for any surgical procedure associated with hollow suspended organs. Dexterity measures, based on multiple characteristic lengths, are presented for procedures corresponding to these manipulation cases. Simulation results of the dual-arm robotic system for ophthalmic surgery are presented for all four manipulation cases. A comparison of this robotic system with current surgical tools shows a significant improvement in intraocular dexterity.

Enabling Technology for Microvascular Stenting in Ophthalmic Surgery

Microstenting is a potentially revolutionary approach to surgical treatment of microvascular retinal disorders that do not resolve using pharmaceutical treatment. This article presents a novel device called a stent deployment unit (SDU) that aims at enabling microstent placement in ophthalmic surgery. The clinical motivation for this work is highlighted in context of microvascular retinal surgery. The proposed SDU is designed for intraocular adjustment of the approach angle and the position of the stent with respect to the retina. The feasibility of this device is experimentally evaluated on chick chorioallantoic membranes and on agar vascular models. Experiments show dependency on the approach angle with respect to the vasculature and on the mobility of the vasculature. Successful placement of stents was achieved in both experimental media. To the best of our knowledge, this pioneering work is the first to demonstrate successful stent deployment in a scale suitable for retinal surgery. We believe that this technique has the promise of enabling effective vascular treatments for blinding conditions such as central and branch retinal vein occlusion.

Analysis of Major Alleles Associated With Age-Related Macular Degeneration in Patients With Multifocal Choroiditis: Strong Association With Complement Factor H

OBJECTIVE To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC). METHODS A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q). RESULTS Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group. CONCLUSIONS Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets.

Subfoveal Pigment Changes in Patients with Longstanding Epiretinal Membranes

PURPOSE To characterize subfoveal changes in patients with longstanding epiretinal membranes (ERM). DESIGN Retrospective study. METHODS Analysis of 123 eyes of 123 consecutive patients who underwent surgery for ERM at the Columbia University Medical Center by a single surgeon (S.C.). Eyes were split into 2 groups: those with a preoperative yellow pigmented foveal spot and those without. The latter group was considered the control group. The primary outcome measures were logarithm of the minimum angle of resolution (logMAR) visual acuity at postoperative months 1 and 3 compared with baseline. Fundus photography, optical coherence tomography (OCT), and autofluorescence images were analyzed. RESULTS We identified 9 eyes with a yellow pigmented spot. All of these eyes exhibited OCT evidence of outer retinal disorganization and hypoautofluorescence. The mean duration of symptoms prior to surgery in these patients was 53 months. The mean duration of symptoms in the control group was 10.7 months. Mean Snellen acuities of the control vs yellow pucker groups were 20/59.7 vs 20/83.5 (P = .041) at baseline; 20/43.3 vs 20/64.8 (P = .006) at postoperative month 1; and 20/34.2 vs 20/50.3 (P = .011) at postoperative month 3. The logMAR magnitude of visual improvement for the yellow pucker vs control groups was not statistically different at either months 1 or 3. Central macular thickness on OCT of patients with yellow pucker decreased from a mean 495 to 395 microns (P = .041). CONCLUSIONS A characteristic yellow macular spot associated with ERM appears to be a sign of chronicity. OCT demonstrates outer retinal disorganization. This feature may portend a worse postoperative visual prognosis.

Post-Marketing Survey of Adverse Events Following Ocriplasmin

BACKGROUND AND OBJECTIVE To study the post-marketing safety profile of ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) as experienced by retinal physicians in the United States. STUDY DESIGN/MATERIALS AND METHODS Two thousand four hundred sixty-five retinal physicians were surveyed regarding their frequency of use of ocriplasmin and reports of ocular adverse events. RESULTS There were 270 respondents (11%) who reported treating 1,056 eyes with ocriplasmin. The reports of adverse events (AE) were as follows: acute decline in visual acuity (16.95%), development of submacular fluid or serous retinal detachment (10.23%), dyschromatopsia (9.09%), progression of vitreomacular traction to macular hole (8.71%), development of retinal detachment (2.65%), development of retinal tear (1.99%), development of afferent pupillary defect (1.80%), electroretinography abnormalities (0.57%), crystalline lens instability (0.38%), and vasculitis (0.28%). CONCLUSION Although the frequency of some ocular AEs reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology and clinical relevance of ocular AEs of ocriplasmin.

Vitrectomy After ocriplasmin for VitreOmacular adhesion Or Macular hole (VAVOOM) study

Background/aims To describe the results of pars plana vitrectomy (PPV) for persistent symptomatic vitreomacular traction (VMT) with or without macular hole (MH) after intravitreal ocriplasmin injection. Methods Multicentre retrospective study of eyes that received intravitreal ocriplasmin between January 2013 and January 2014 for symptomatic VMT with or without MH, and then went on to PPV (ocriplasmin-treated group) for persistent pathology, compared with a control group of patients with symptomatic VMT with or without MH who were offered ocriplasmin injection but proceeded directly to PPV (PPV-only group). Intraoperative characteristics, visual acuity (VA) outcomes and spectral-domain optical coherence tomography images were reviewed for the two groups. Primary outcome measure was VA after PPV. Results 51 eyes of 51 patients underwent PPV after receiving ocriplasmin, and 22 eyes of 22 patients proceeded directly to PPV. Although VA was significantly better at all time points in the PPV-only compared with the ocriplasmin-treated group, at 3 and 6 months after PPV both groups had similar amount of visual improvement. Both groups had similar rates of pathology resolution; 50/51 (98%) eyes in the ocriplasmin group and 22/22 (100%) eyes in the PPV-only group had release of VMT and/or MH closure after PPV. The two groups had similar PPV-related complication rates. Conclusions Eyes with persistent symptomatic VMT and/or MH have similarly high rates of pathology resolution as well as similar VA gains regardless of whether they received ocriplasmin prior to PPV.