Benjamin P. Nicholson

A review of clinical trials of anti-VEGF agents for diabetic retinopathy

BackgroundDiabetic retinopathy (DR) is a leading cause of vision loss in the working-age population worldwide. Many observational and preclinical studies have implicated vascular endothelial growth factor (VEGF) in the pathogenesis of DR, and recent successes with anti-VEGF therapy for age-related macular degeneration (AMD) have prompted research into the application of anti-VEGF drugs to DR. Here we review the numerous early studies that suggest an important potential role for anti-VEGF agents in the management of diabetic retinopathy.ConclusionsFor diabetic macular edema, phase II trials of intravitreal pegaptanib and intravitreal ranibizumab have shown short-term benefit in visual acuity. Intravitreal bevacizumab also has been shown to have beneficial short-term effects on both visual acuity and retinal thickness. For proliferative diabetic retinopathy (PDR), early studies suggest that intravitreal bevacizumab temporarily decreases leakage from diabetic neovascular lesions, but this treatment may be associated with tractional retinal detachment (TRD). Furthermore, several studies indicate that bevacizumab is likely to prove a helpful adjunct to diabetic pars plana vitrectomy (PPV) for TRD. Finally, three small series suggest a potential beneficial effect of a single dose of bevacizumab to prevent worsening of DME after cataract surgery. Use of anti-VEGF medications for any of these indications is off-label. Despite promising early reports on the safety of these medications, we eagerly await the results of large, controlled trials to substantiate the safety and efficacy of anti-VEGF drugs for diabetic retinopathy.

Evaluation of Fluocinolone Acetonide Sustained Release Implant (Retisert) Dissociation during Implant Removal and Exchange Surgery

PURPOSE To characterize the phenomenon of dissociation of the 2 components of the sustained-release fluocinolone acetonide implant (Retisert; Bausch & Lomb) during removal or exchange procedures, or both, and to evaluate outcomes after these events. DESIGN Retrospective, observational case series. METHODS Retrospective review of 27 consecutive sustained-release fluocinolone acetonide implant (Retisert) exchanges or removals between 2001 and 2010 at the Cole Eye Institute. All patients had received the implant as treatment for noninfectious uveitis. Preoperative and postoperative characteristics were analyzed, and operative reports were reviewed to characterize the effects of intraoperative implant dissociation. RESULTS Twenty-seven sustained-release fluocinolone acetonide implant (Retisert) exchange or removal surgeries were performed by 3 surgeons in 20 eyes of 19 patients. Of these 27 procedures, dissociation of the implant strut from the drug-containing cup occurred in 11 eyes (40.7%). Retrieval of the dislocated cup led to intraoperative complications, including posterior retinal tear (n = 1) and limited suprachoroidal hemorrhage (n = 1). The length of time that the implant resided in the eye correlated significantly with cup dissociation. Dissociated implants resided a mean of 47.4 months, whereas intact implants resided a mean of 32.5 months (P = .0032). There was no long-term or short-term vision loss attributed to intraoperative implant dissociation. CONCLUSIONS Sustained-release fluocinolone acetonide implant (Retisert) dissociation is a common occurrence in exchange or removal procedures, or both. The longer an implant resided in the eye, the greater the tendency toward dissociation. Preparation for this complication should be contemplated in any implant removal or exchange procedure.

Efficacy of the intraoperative relaxed muscle positioning technique in thyroid eye disease and analysis of cases requiring reoperation

PURPOSE In the relaxed muscle positioning technique of treating strabismus for thyroid eye disease (TED), the most restricted muscles, as determined by preoperative assessment of ductions and intraoperative forced ductions, are recessed to the positions where they rest freely on the globe without tension. The purpose of this technique is to identify preoperative characteristics that are predictive of reoperation and evaluate outcomes. METHODS Retrospective review of patients with TED who underwent strabismus surgery using the relaxed muscle positioning technique between 1999 and 2009. Preoperative characteristics; surgical outcomes at 2, 6, and 12 months; and the outcomes of reoperations were evaluated. Outcomes were categorized as excellent (no diplopia in primary and reading gazes without prisms), good (diplopia requiring ≤10(Δ) correction), and poor (persistent diplopia in primary or reading gazes despite prism or attempted prism correction). RESULTS Of 63 TED patients treated during the study period, 58 met inclusion criteria. Of these, 45 patients (78%) underwent only one strabismus surgery; 10 (17%), 2 surgeries; and 3 (5%), 3. Excellent outcomes were achieved in 48 (83%), good in 4 (7%), and poor in 6 (10%). Mean follow-up was 12.1 months (range, 1.5 months to 11.5 years). There was an increased likelihood for reoperation in patients with multiple treatment modalities for Graves disease (P = 0.03) and larger horizontal deviations (P = 0.03). CONCLUSIONS The intraoperative relaxed muscle positioning technique improved ocular alignment and relieved diplopia in most patients with dysthyroid strabismus. Patients with more severe disease were more likely to require reoperation.

Congenital optic nerve malformations

Aplasia of the optic nerve is characterized by complete absence of the optic nerve, absence of retinal vessels, and no light perception vision. It was first described in 1854 by von Graefe. Only a few dozen cases have been reported in the literature. Most have been unilateral. Aplasia of the optic nerve is congenital, and its etiology remains poorly understood. There is no known sex or racial predilection. No abnormal karyotypes have been reported. Two patients with aplasia were found to have PAX6 polymorphisms, but no familial cases have been reported. Others have had in utero exposures including acetone, maternal viral infection, and maternal tobacco use. Aplasia of the optic nerve has been induced in experimental animals by treating with hypoglycemic sulfonamides, creating folic acid deficiency, exposing fetuses to x-ray radiation, and treatment with actinomycin D. Some have argued that a local failure of mesoderm leads to a lack of normal vascular development within the optic nerve. Most pathologic specimens lack retinal ganglion cells, but a 3-day-old autopsy in 1 case of bilateral aplasia showed undifferentiated ganglion cells lacking axons and dendrites. Failure of these cells to elaborate axons may be the mechanism of this malformation. Alternatively, nerve fiber misdirection and subsequent atrophy could also lead to this phenotype. Pathologic studies have shown that the neural crest-derived optic nerve sheath tends to be present and connected to the back of these eyes despite the lack of nerve tissue. The retina tends to be dysplastic with rosette formation.

Idiopathic dural optic nerve sheath calcification

A 58-year-old African American man presented to the ophthalmic oncology clinic after referral from a community physician who noted bilateral calcified lesions of the optic nerves on a CT scan performed for dizziness (figure 1). The patient reported no recent change in his vision and had no complaints. His dizziness had resolved spontaneously by the time of our encounter. He denied headache, visual field changes and diplopia. He reported having a normal eye exam 2 years previously. His past medical history included only hyperlipidaemia and osteoarthritis. He denied any history of malignancy or kidney disease. Figure 1 CT scan of the brain performed for dizziness shows bilateral calcifications along the optic nerve within the orbit (A). The study also showed extensive intracranial dural calcification (B). Physical examination revealed 20/15 vision bilaterally, normal intraocular pressures, equal and reactive pupils with no afferent pupillary defect, normal motility and alignment and no proptosis. Both optic nerves had a normal appearance with no swelling, pallor or cupping. The remainder of his funduscopic examination was normal. There were no visual field defects. Colour vision was assessed with Ishihara plates and was normal. He then underwent B-scan ultrasonography to assess his optic nerves (figure 2). …

Bevacizumab and diabetic vitrectomy.

Diabetic retinopathy is a leading cause of blindness in working-age adults in many developed nations. Proliferative diabetic retinopathy (PDR) is an advanced stage of the disease that can result in vitreous hemorrhage or tractional retinal detachment (TRD). These manifestations of PDR cause severe vision loss. The Diabetic Retinopathy Study established panretinal photocoagulation (PRP) as the standard of care for high-risk PDR. However, some patients present late after developing vitreous hemorrhage or TRD, and other eyes progress despite treatment or are not amenable to laser therapy. In these cases, vitrectomy may be necessary to restore vision. Numerous recent studies have suggested that off-label, intravitreal injection of bevacizumab in the perioperative period facilitates vitrectomy in these circumstances.

Wide-Field Imaging in Uveitis

Wide-field imaging technologies have become increasingly utilized in the practice of uveitis, and initial descriptive studies suggest that wide-field imaging may be helpful for many inflammatory and infectious ocular diseases. A variety of commercially available imaging products offer wide-field capability, and each system has distinct advantages and disadvantages. Wide-field cameras may be able to capture color images, fluorescein angiographic images, autofluorescence images, and indocyanine green angiographic images. This chapter contains a review of the uveitis literature and a discussion of notable findings and potential uses of each of these modalities. However, as no randomized trial has studied the impact of wide-field imaging on uveitis treatment or patient outcomes, caution is necessary when considering treatment decisions based on wide-field imaging findings.