Ranibizumab is a potential prophylaxis for proliferative vitreoretinopathy, a nonangiogenic blinding disease.

Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina. Three classes of growth factors [vascular endothelial growth factor A (VEGF-A), platelet-derived growth factors (PDGFs), and non-PDGFs (growth factors outside of the PDGF family)] are relevant to PVR pathogenesis because they act on PDGF receptor α, which is required for experimental PVR and is associated with this disease in humans. We discovered that ranibizumab (a clinically approved agent that neutralizes VEGF-A) reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The apparent mechanism of ranibizumab action involved derepressing PDGFs, which, at the concentrations present in PVR vitreous, inhibited non-PDGF-mediated activation of PDGF receptor α. These preclinical findings suggest that available approaches to neutralize VEGF-A are prophylactic for PVR, and that anti-VEGF-based therapies may be effective for managing more than angiogenesis- and edema-driven pathological conditions.

Closed globe macular injuries after blasts in combat.

PURPOSE: To describe the macular findings after closed globe ocular injuries sustained from blasts. METHODS: A retrospective chart review from February 2003 to March 2010 of all soldiers with closed globe ocular injuries sustained during combat with macular findings of trauma on examination was completed. RESULTS: There were 36 eyes that met the inclusion criteria. The mean age of the soldiers was 29.5 years and 97% were men. The average follow-up time was 18.6 months. Improvised explosive device blasts accounted for 86% of injuries. Forty-five percent of soldiers had bilateral ocular injuries. Eight of 36 eyes (22.2%) developed a macular hole. One eye had spontaneous closure and five eyes underwent surgical repair. There was a range of macular findings from retinal pigment epitheliopathy alone to retinal pigment epitheliopathy with full-thickness atrophy. Eight eyes (22.2%) had macular scarring on examination but no optical coherence tomography study. One eye (2.8%) developed phthisis bulbi. Fifteen eyes (42%) had an orbital fracture. Seven eyes (19%) sustained optic neuropathy. CONCLUSION: Closed globe injuries after blasts resulted in a spectrum of macular findings. The integrity of the foveal inner segment/outer segment junction was the most important retinal factor in visual outcomes. Orbital fractures were not found to be a risk factor for developing optic neuropathy and may improve visual outcomes. The rate of long-term complications is unknown, and it is important for ophthalmologists to follow these patients closely.

Perforating globe injuries during operation Iraqi Freedom.

OBJECTIVE: To report the injury patterns associated with perforating (through-and-through) injuries of the globe and the visual impact of these injuries on patients with combat ocular trauma (COT) seen at Walter Reed Army Medical Center (WRAMC) from March 2003 through October 2006. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Sixty-five eyes of 61 United States military soldiers deployed during Operation Iraqi Freedom sustaining perforating globe injuries and treated subsequently at WRAMC. INTERVENTION: Principal procedures included enucleation and 20-gauge 3-port pars plana vitrectomy with or without intraocular foreign body removal. MAIN OUTCOME MEASURES: Final visual acuity and rates of proliferative vitreoretinopathy, enucleation, and endophthalmitis. RESULTS: Average patient age was 29 years, with an average of 200 days of postinjury follow-up (median, 97 days; range, 4-1023 days). Nineteen patients confirmed the use of eye protection at the time of injury, whereas 25 patients did not use eye protection. The median presenting visual acuity at WRAMC was no light perception (range, no light perception to hand movements). Twenty-five patients underwent primary enucleation, 1 was eviscerated, and 12 patients underwent secondary enucleation within 2 weeks of surgery. Of 19 patients undergoing pars plana vitrectomy, median visual acuity at presentation was light perception and the median final visual acuity was counting fingers, whereas 4 eyes (21%) achieved final visual acuity of better than 20/200, and in 11 (61%) of 17, proliferative vitreoretinopathy developed over a follow-up of at least 6 months. There were no cases of endophthalmitis or sympathetic ophthalmia. Neither mechanism of injury nor timing of surgery correlated with favorable outcomes. However, entry and exit wounds localized to the anterior half of the globe were associated with favorable anatomic outcome (P<0.005, Fisher exact test, 2-tailed) and visual outcome (P = 0.041, Fisher exact test, 2-tailed). CONCLUSIONS: Perforating globe injuries associated with COT generally result in poor visual and anatomic outcomes despite surgical intervention. Prophylactic measures, such as eye protection, are helpful in reducing the likelihood of perforating injuries; however, novel surgical and pharmacologic therapies will be required to improve the functional and anatomic outcomes of these devastating injuries.

Evaluation of digital fundus images as a diagnostic method for surveillance of diabetic retinopathy.

OBJECTIVE: The goal was to evaluate a digital imaging system for diagnosing and grading diabetic retinopathy (DR) and cystoid macular edema (CME). METHODS: A single 45 degrees, nonmydriatic, digital color photograph was taken of 231 eyes of 120 patients with diabetes mellitus. The images were graded for DR and CME by a remote ophthalmologist, and the results were compared with dilated ophthalmoscopy performed by a retina specialist. RESULTS: For DR, the level of agreement between digital image review and ophthalmoscopy was moderate (kappa = 0.44). The sensitivity and specificity of digital image review were 0.60 and 1.00, respectively. For CME, the level of agreement was moderate (kappa = 0.60). The sensitivity and specificity of digital image review were 0.60 and 0.99, respectively. CONCLUSION: A single 45 degrees, nonmydriatic, digital image is not reliable as the sole modality for DR screening. However, with modifications, it may be useful where access to an experienced ophthalmologist is limited.

A pilot study of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema.

OBJECTIVE: To evaluate the biologic activity of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema (DME) and to report any associated adverse events. DESIGN: Single-center, open-label, dose-escalating pilot study. PARTICIPANTS: A total of 10 eyes of 10 patients (mean age, 69.3 years [range, 59-81]) with DME involving the center of the macula and best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400. INTERVENTION: Three intravitreal injections of ranibizumab (0.3 mg or 0.5 mg each injection) administered on day 0, month 1, and month 2, and observation until month 24. MAIN OUTCOME MEASURES: Primary end points were the frequency and severity of ocular and systemic adverse events. Secondary end points were BCVA and measurement of retinal thickness by optical coherence tomography. RESULTS: Of the 10 patients enrolled, 5 received 0.3-mg and 5 received 0.5-mg ranibizumab. Intravitreal injections of ranibizumab were well tolerated. No systemic adverse events were reported. Five occurrences of mild to moderate ocular inflammation were reported. At month 3, 4 of 10 patients gained > or =15 letters, 5 of 10 gained > or =10 letters, and 8 of 10 gained > or =1 letters. At month 3, the mean decrease in retinal thickness of the center point of the central subfield was 45.3+/-196.3 microm for the low-dose group and 197.8+/-85.9 microm for the high-dose group. CONCLUSIONS: Ranibizumab appears to be a well-tolerated therapy for patients with DME. This pilot study demonstrates that ranibizumab therapy has the potential to maintain or improve BCVA and reduce retinal thickness in patients with center-involved clinically significant DME.

Visual prosthetic device for bilateral end-stage macular degeneration.

Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life.

Hydroxychloroquine retinopathy after short-term therapy.

PURPOSE: To report an unusual case of hydroxychloroquine toxicity after short-term therapy. METHODS: Observational case report. RESULTS: A 56-year-old woman presented to the Ophthalmology Clinic at Walter Reed Army Medical Center (WRAMC) with a 6-month history of gradually decreasing vision in both eyes. The patient had been taking hydroxychloroquine for the preceding 48 months for the treatment of rheumatoid arthritis. Examination of the posterior segment revealed bilateral "bull's eye" macular lesions. Fundus autofluorescence revealed hyperfluorescence of well-defined bull's eye lesions in both eyes. Optical coherence tomography revealed corresponding parafoveal atrophy with a loss of the retinal inner segment/outer segment junction. Humphrey visual field 10-2 white showed significant central and paracentral defects with a generalized depression. The patient was on a standard dose of 400 mg daily, which was above her ideal dose. The patient had no history of kidney or liver dysfunction. There were no known risk factors but there were several possible confounding factors. The patient was started on high-dose nabumetone, a nonsteroidal antiinflammatory drug, at the same time she was started on hydroxychloroquine. She also reported taking occasional ibuprofen. CONCLUSION: Retinal toxicity from chloroquine has been recognized for decades with later reports showing retinopathy from long-term hydroxychloroquine (Plaquenil) use for the treatment of antiinflammatory diseases. Hydroxychloroquine is now widely used and retinal toxicity is relatively uncommon. However, it can cause serious vision loss and is usually irreversible. The risk of hydroxychloroquine toxicity rises to nearly 1% with a total cumulative dose of 1,000 g, which is ∼5 years to 7 years of normal use. Toxicity is rare under this dose. For this reason, the American Academy of Ophthalmology has revised its recommendations such that annual screenings begin 5 years after therapy with hydroxychloroquine has begun unless there are known risk factors. This case report confirms the need for a baseline examination and annual ophthalmologic screening for patients taking hydroxychloroquine at a dose higher than the recommended dosage. It is also reasonable to consider annual examinations in patients taking high-dose nonsteroidal antiinflammatory drugs from the initiation of the medication.

Multi-purpose extraocular forceps for small-gauge pars plana vitrectomy.

A multi-purpose titanium forceps has been developed for small-gauge pars plana vitrectomy surgery. These forceps were designed to provide the vitreoretinal surgeon with a single tool for the extraocular manipulations that are necessary for the placement and removal of 23- and 25-gauge trochars for small-incision, sutureless pars plana vitrectomy surgery. The forceps has been designed to allow for the atraumatic manipulation of the conjunctiva, measurement of distance from the limbus, and a strong purchase of the trochar for both its fixation and removal.

Visual and anatomic outcomes of vitrectomy with temporary keratoprosthesis or endoscopy in ocular trauma with opaque cornea.

BACKGROUND AND OBJECTIVE: To examine the outcomes of vitrectomy in ocular trauma with opaque cornea. PATIENTS AND METHODS: This retrospective study included 17 eyes of 16 patients who underwent vitrectomy with temporary keratoprosthesis or endoscopy at Walter Reed Army Medical Center, Washington, DC, from March 2003 to October 2010. RESULTS: A temporary keratoprosthesis was used in 8 eyes (47%) and endoscopy in 9 eyes (53%). Overall, the number of eyes with visual acuity of 20/200 or better improved from 0 at baseline to 5 (29%) at 6 months. The number of eyes with retinal detachment also improved from 10 (59%) at baseline to 3 (18%) at 6 months. CONCLUSION: Vitrectomy may be safely performed in ocular trauma with opaque cornea using a temporary keratoprosthesis or endoscopy with comparable outcomes. Endoscopy allows earlier diagnosis and treatment of occult pathology and requires less time and fewer procedures to implement than the temporary keratoprosthesis.