Residual edema evaluation with ranibizumab 0.5 mg and 2.0 mg formulations for diabetic macular edema (REEF study).

PURPOSE: To compare the efficacy of ranibizumab 0.5-mg and 2.0-mg intravitreal injections for persistent diabetic macular edema (DME) previously treated with bevacizumab. METHODS: In all, 43 patients with residual center-involved DME following intravitreal bevacizumab were included in this 12-month prospective, nonrandomized, multicenter study. Enrolled patients received three monthly ranibizumab 0.5-mg injections. At month 3, patients with residual macular edema switched to three monthly injections of ranibizumab 2.0-mg. Assessments included monthly visual acuity and spectral-domain optical coherence tomography. RESULTS: Mean visual acuity improved by +6.4 letters at month 3 and +8.8 letters at month 6. Mean central subfield thickness (CST) decreased by -113 µm at month 3 and -165 µm at month 6. Before enrollment, 29/43 (67.4%) patients showed <10% CST reduction following monthly bevacizumab treatment. After three monthly ranibizumab 0.5-mg injections, 22/29 (75.9%) patients showed >10% reduction in CST, whereas 6 showed <10% reduction. Of these six, three (50%) showed >10% reduction in CST after switching to three monthly ranibizumab 2.0-mg doses. No serious adverse events were observed to month 6. CONCLUSION: Ranibizumab 0.5-mg or 2.0-mg may improve visual and anatomic outcomes in patients with DME who demonstrated minimal or no response to bevacizumab therapy. Moreover, increased dosage of ranibizumab (2.0-mg) may provide additional benefit over ranibizumab 0.5-mg in some patients. However, 2.0-mg ranibizumab is not currently commercially licensed or available.

Anti-VEGF therapy: comparison of current and future agents.

With the identification of vascular endothelial growth factor (VEGF) and the confirmation of its pathophysiologic link to retinal and choroidal angiogenesis, numerous agents have been designed to inhibit its activity. It is noteworthy that anatomic and visual benefits have been associated with the use of anti-VEGF agents such as pegaptanib (Macugen) and to a greater extent, ranibizumab (Lucentis) and bevacizumab (Avastin), particularly in the management of neovascular age-related macular degeneration (AMD). Clinical trials and case series have confirmed the utility of these agents. However, shortcomings of the current drugs such as short half-life, intraocular dosing, limited effectiveness in some patients, and potential systemic side effects continue to drive the development of new agents. In this article, we review current anti-VEGF therapies and discuss future developments.

Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy.

AIMS: The aim of this study was to report the development or progression of tractional retinal detachment (TRD) after the injection of intravitreal bevacizumab (Avastin) used as an adjuvant to vitrectomy for the management of severe proliferative diabetic retinopathy (PDR). METHODS: The clinical charts of patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 mg bevacizumab before vitrectomy for the management of PDR were reviewed. RESULTS: Eleven eyes (patients) out of 211 intravitreal injections (5.2%) that developed or had progression of TRD were identified. All eyes had PDR refractory to panretinal photocoagulation (PRP). Nine patients had type 1 diabetes mellitus (DM), and two patients had type 2 DM. Patients had a mean age of 39.5 years (range 22-62 years). In the current study, all patients used insulin administration and had poor glycaemic control (mean HbA(1c) 10.6%). Time from injection to TRD was a mean of 13 days (range 3-31 days). Mean best correct visual acuity (BCVA) at TRD development or progression was logarithm of the minimal angle of resolution (LogMAR) 2.2 (range 1.0-2.6) (mean Snellen equivalent hand motions; range 20/200 to light perception), a statistically significant worsening compared with baseline BCVA (p<0.0001). Eight eyes underwent vitrectomy and three patients refused or were unable to undergo surgery. The final mean BCVA after surgery was LogMAR 0.9 (range 0.2-2.0) (mean Snellen equivalent 20/160; range 20/32 to counting fingers), a statistically significant improvement compared with TRD BCVA (p = 0.002). CONCLUSIONS: TRD may occur or progress shortly following administration of intravitreal bevacizumab in patients with severe PDR.

Airbags and eye injuries: epidemiology, spectrum of injury, and analysis of risk factors.

Although airbags measurably reduce the overall risk of injury to adults (including eye injury), and death from motor vehicle accidents, injuries attributed to airbag deployment have been reported. To identify reported cases of ocular trauma related to airbag deployment, a MEDLINE search from 1991 to 2000 was performed. A total of 263 injuries in 101 patients were identified. Patient demographics, details of the accident, specific ocular structures injured, and visual outcomes when available where tabulated and analyzed. The most common of these affect the eyes. Damage to the orbit and virtually every ocular and adnexal structure has been seen. Although most injuries are self-limited and do not significantly compromise vision, some result in severe, permanent visual loss. Most common is damage to anterior structures due to either blunt, contusive forces and/or chemical injury. Posterior segment trauma is less common but generally more visually devastating because of the involvement of the retina or optic nerve. Data are not available to determine whether the wearing of eyeglasses or previous intraocular surgery affects the nature, severity, or outcome of these injuries. Awareness of the spectrum of airbag-associated ocular trauma will help physicians recognize these problems early and optimize their management. Data derived from analyses of these injuries will be critical to the development of safer, more effective devices.

Open globe injuries in children: a retrospective analysis.

PURPOSE: To study the outcome of open globe injuries in patients aged <14 years and compare the results between patients who presented approximately 30 years ago and a recent series. METHODS: Between January 1970 and January 1993, 180 eyes of children who presented with an open globe injury were retrospectively analyzed. Patients were divided into two groups. One group of children underwent treatment of an open globe injury between January 1970 and December 1981 (group A) and another between December 1985 and January 1993 (group B). Main outcome measures studied were final visual acuity and enucleation rates. Risk factors studied included age, race, sex, visual acuity, type of trauma, and various injury characteristics at presentation. RESULTS: The factors associated with visual outcomes included: age, type of injury, wound size, initial visual acuity, and retinal detachment. Final visual outcome and enucleation rates were not significantly different between the older series (group A) and the recent series (group B). Lenticular damage, location, posterior extent of the injury, and presence of an intraocular foreign body had been significant prognostic factors in the older series, but were not statistically associated with the prognosis in the recent series. CONCLUSION: The nature of the injury and the patient's age are the main determining factors in the outcome of open globe injuries in children.

Macular translocation: unifying concepts, terminology, and classification.

PURPOSE: To describe some unifying concepts, terminology, and classification of macular translocation so as to facilitate communication within the scientific community. METHODS: A panel of ophthalmologists with expertise in macular translocation reviewed available data and developed some unifying concepts, terminology, and classification of macular translocation. RESULTS: Macular translocation may be defined as any surgery that has a primary goal of relocating the central neurosensory retina or fovea intraoperatively or postoperatively specifically for the management of macular disease. It may be classified according to the size of the retinotomy and, where applicable, the technique of chorioscleral shortening used. The direction of macular translocation is denoted by the movement of the neurosensory macula relative to the underlying tissues. Effective macular translocation may be defined as successful intraoperative or postoperative relocation of the fovea overlying a subfoveal lesion to an area outside the border of the lesion. The concepts of minimum desired translocation and median postoperative foveal displacement can give some useful idea of the likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of a common standardized terminology for macular translocation will facilitate communication within the scientific community and enhance further research in this area. However, the definitions, terms, classification, and concepts concerning macular translocation are likely to continue to evolve as macular translocation undergoes further modifications and refinements.

Limited macular translocation for the management of subfoveal retinal pigment epithelial loss after submacular surgery.

PURPOSE: To report a case of subfoveal retinal pigment epithelial (retinal pigment epithelium) loss after submacular surgery managed successfully by limited macular translocation. METHODS: Case report. RESULTS: A 28-year-old woman presented with a visual acuity of 20/100 caused by subfoveal choroidal neovas-cularization secondary to ocular histoplasmosis syndrome. Submacular resection of the choroidal neovascularization was complicated by inadvertent retinal pigment epithelium loss from beneath the foveal center. She underwent limited macular translocation 5 days after the initial surgery and had successful displacement of the fovea to an area inferior to the retinal pigment epithelium defect. Her visual acuity was 20/60 4 months postoperatively. CONCLUSION: This report demonstrates the feasibility of using limited macular translocation for the management of eyes with central retinal pigment epithelium defect after submacular surgery and extends the clinical indications for limited macular translocation.

Initial experience of inferior limited macular translocation for subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration.

PURPOSE: To report our initial experience of inferior limited macular translocation in patients with subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration. METHODS: We conducted a retrospective study of 23 eyes of 22 patients with choroidal neovascularization involving the foveal center secondary to pathologic myopia (11 eyes), ocular histoplasmosis syndrome (four eyes), angioid streaks (four eyes), idiopathic neovascularization (three eyes), and multifocal choroiditis (one eye), in which the fovea was moved inferiorly by means of limited macular translocation surgery. The mean preoperative best-corrected visual acuity was 20/150, and in five of 23 eyes (21.7%) the visual acuity was 20/80 or better. The major outcome measures were preoperative and postoperative visual acuity, postoperative foveal displacement, and complications related to the surgery. RESULTS: The mean postoperative follow-up was 10.82 months (range, 6 to 18 months). Postoperative best-corrected visual acuity improved by 2 or more Snellen lines of visual acuity in 11 of 23 eyes (47.82%), remained within 1 line in seven of 23 eyes (30.43%), and worsened 2 or more lines of vision in five of 23 eyes (21.74%). The mean postoperative best-corrected visual acuity was 20/100, and in 12 of the 23 eyes (52.17%) the visual acuity achieved was 20/80 or better. Retinal detachment was the most frequent complication and occurred in six eyes (26%). CONCLUSIONS: Our initial experience with limited macular translocation shows that this treatment modality offers the potential to improve visual function in some eyes with subfoveal choroidal neovascularization secondary to myopia, ocular histoplasmosis syndrome, angioid streaks, idiopathic neovascularization, and multifocal choroiditis. Although longer and more complete follow-up is needed, the results of this initial series warrant further studies to define the precise role of macular translocation in the management of these conditions.

Complications associated with limited macular translocation.

PURPOSE: To report the ocular complications associated with the limited macular translocation procedure. METHODS: Retrospective review of 153 consecutive eyes of 151 patients that had the limited macular translocation procedure for subfoveal choroidal neovascularization between April 1996 and February 1999. The major study variables investigated included the incidence of specific ocular complications and their impact on visual acuity at 3 months after the surgery. In addition, baseline patient characteristics and operative factors were evaluated to determine whether they were significant risk factors for the development of an ocular complication. The existence of a surgical procedure learning process was investigated. RESULTS: One hundred forty-one (92.15%) of 153 eyes achieved at least 3-month follow-up. At least one complication occurred in 53 of 153 eyes (34.6%) and in 51 of these 53 eyes (96. 22%) the complications occurred before 3 months of postoperative follow-up. The intraoperative and postoperative complications included retinal detachment (17.4%), retinal breaks (13.4%), macular holes (7.8%), macular fold (4.6%), and intraocular hemorrhage (vitreous, subretinal, or choroidal; 9.2%). Eyes that developed retinal detachment, subretinal hemorrhage, and macular fold had significantly more loss of visual acuity than eyes without each of these complications (P =.0001, P =.038, and P =.027, respectively). The presence of predominantly classic choroidal neovascularization, the occurrence of an intraoperative retinal break, any intraocular hemorrhage, or macular fold formation were significantly associated with retinal detachment (P =.021, P =.025, P =.013, and P =.014, respectively). The incidence of any complication, retinal detachment, and hemorrhage significantly decreased during the study period, suggesting a learning process (P =.03, P =.006, P =.027, respectively). CONCLUSIONS: A variety of ocular complications can occur during or after limited macular translocation, and some are associated with reduced postoperative visual acuity. Improved surgical techniques and experience may significantly reduce the incidence of these complications.

Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To review a series of patients with age-related macular degeneration undergoing limited macular translocation for the treatment of subfoveal choroidal neovascularization, to determine short-term visual acuity outcomes, to measure amounts of attainable retinal movement, and to identify prognostic factors. METHODS: A retrospective review was conducted on a consecutive series of patients undergoing inferior limited macular translocation with scleral imbrication for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. The main outcome measures investigated were distance of macular translocation, visual acuity at 3 and 6 months after surgery, change in visual acuity from baseline, and the development of intraoperative and postoperative complications. Univariate and multivariate analyses of a number of potential prognostic factors were undertaken. RESULTS: Macular translocation was achieved in all 102 eyes (101 patients) included in this study. The range of movement varied from 200 to 2,800 microm with a median movement of 1, 200 microm. Nearly 33% of the study group achieved a visual acuity better than 20/100 at 3 months, and 49% achieved this vision at 6 months. At 3 and 6 months, 37% and 48% of the study group, respectively, experienced 2 or more lines of improvement on visual acuity testing, and by 6 months 16% experienced greater than 6 lines of visual improvement. Good baseline vision, achieving the desired amount of macular translocation, a greater amount of macular translocation, and recurrent choroidal neovascularization at baseline were associated with better visual acuities at 3 and 6 months. Poor preoperative vision and the development of complications were associated with worse vision at 3 and 6 months. CONCLUSIONS: Limited macular translocation is a technically feasible procedure that can lead to significant visual improvement and good visual acuity in some patients presenting with subfoveal choroidal neovascularization associated with age-related macular degeneration. A randomized prospective clinical trial of this surgical technique is warranted.

Age-related macular degeneration and risk factors for the development of choroidal neovascularization in the fellow eye.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world. Most of the severe vision loss associated with AMD is due to the development of choroidal neovascularization (CNV). The specific causes of AMD and in particular, its neovascular phase, remain uncertain. During the past two decades a number of large prospective clinical trials, observational epidemiologic studies, and population-based cohort studies have furthered our understanding of this blinding ocular condition. The Macular Photocoagulation Study has received praise for its many contributions in the laser treatment of neovascular complications of AMD; however, these trials have made other significant contributions by helping to better define the natural history of AMD, and in particular, risk factors for the development of CNV in eyes with non-neovascular disease. This type of information may provide significant clues for researchers regarding disease pathogenesis and identify a high-risk group in whom to target new treatment strategies. For patients currently diagnosed with macular degeneration, this information can lead to a better understanding of their condition and a more accurate prognosis of their ocular health and vision status. This article reviews information from a variety of sources to investigate incidence rates and risk factors for the development of CNV in the fellow eye of patients with AMD and unilateral neovascular maculopathy.

A system for classifying mechanical injuries of the eye (globe). The Ocular Trauma Classification Group.

PURPOSE: To develop a classification system for mechanical injuries of the eye. METHODS: The Ocular Trauma Classification Group, a committee of 13 ophthalmologists from seven separate institutions, was organized to discuss the standardization of ocular trauma classification. To develop the classification system, the group reviewed trauma classification systems in ophthalmology and general medicine and, in detail, reports on the characteristics and outcomes of eye trauma, then established a classification system based on standard terminology and features of eye injuries at initial examination that have demonstrated prognostic significance. RESULTS: This system classifies both open-globe and closed-globe injuries according to four separate variables: type of injury, based on the mechanism of injury; grade of injury, defined by visual acuity in the injured eye at initial examination; pupil, defined as the presence or absence of a relative afferent pupillary defect in the injured eye; and zone of injury, based on the anteroposterior extent of the injury. This system is designed to be used by ophthalmologists and nonophthalmologists who care for patients or conduct research on ocular injuries. An ocular injury is classified during the initial examination or at the time of the primary surgical intervention and does not require extraordinary testing. CONCLUSIONS: This classification system will categorize ocular injuries at the time of initial examination. It is designed to promote the use of standard terminology and assessment, with applications to clinical management and research stud ies regarding eye injuries.

Quantitative measurement of the effects of caffeine and propranolol on surgeon hand tremor.

OBJECTIVE: To quantitatively measure the effects of caffeine and propranolol, a nonselective beta-blocking agent, on surgeon hand tremor during simulated vitreoretinal microsurgery. METHODS: Seventeen ophthalmic surgeons were tested on 3 separate days. On each day, subjects ingested 200 mg of caffeine, 10 mg of propranolol hydrochloride, or gelatin placebo. The drugs were administered as part of a double-masked, placebo-controlled trial. Hand tremor was measured using the Microsurgery Advanced Design Laboratory Stability, Activation, and Maneuverability tester (MADSAM), a high-resolution, noncontact position tracking system. RESULTS: The average percent magnitude changes from baseline tremor measurements were +15%, +31%, and -22% for placebo, caffeine, and propranolol groups, respectively. Analysis of variance techniques accounting for effects of individuals, drugs, and day order demonstrated that only drug effects on percent magnitude change of tremor were statistically significant (P = .01, F test). Detailed comparisons of the 2 drug groups with the placebo group revealed that, after adjusting for individual and order effects, only the mean decrease in tremor due to ingestion of propranolol was a statistically significant trend (P = .03, F test). Although caffeine caused a larger mean increase in percent magnitude change in tremor than placebo, this trend was not statistically significant (P = .34, F test). The evaluation of systemic physiologic measurements showed that there were statistically significant drug effects on percent change in systolic (P < .001, F test) and diastolic (P = .002, F test) blood pressure and pulse rate (P = .002, F test). Individual and day order effects were not significant. No adverse side effects were observed or reported in our test subjects. CONCLUSION: Physiologic surgeon hand tremor can be decreased by the oral intake of a low dose of propranolol.

Open-globe injury. Update on types of injuries and visual results.

PURPOSE: The purpose of the study is to evaluate a recent series of patients who presented with open-globe injuries and to compare this series with a previous series collected at the authors' institution to determine whether prognostic factors or visual outcomes have changed. METHODS: A retrospective review of 290 eyes of consecutive patients who presented to the Wilmer Ophthalmological Institute with open-globe injuries between December 1985 and January 1993 (group B) was compared with a series of 476 eyes with open-globe injury treated and evaluated at this institute between January 1970 and December 1981 (group A). For comparison, the outcomes evaluated included rates of enucleation and final visual acuity. RESULTS: Several factors identified previously in group A to correlate with visual outcomes also were found to correlate significantly (P < 0.001) with visual outcome in group B, including: (1) type of injury, (2) location and extent of injury, (3) initial visual acuity, (4) presence of an afferent pupillary defect, (5) lenticular involvement, (6) vitreous hemorrhage, and (7) type of intraocular foreign body. Overall visual outcomes differed significantly between the groups (P = 0.02). The incidence of enucleation was lower in group B (24%) than in group A (30%). However, the percentage of patients who achieved ambulatory visual acuity (5/200) or better was similar in both groups (57%, group A versus 55%, group B). CONCLUSION: Prognostic factors identified previously proved valid in this recent series. Visual outcomes have improved at this institution in the last 20 years for patients with severe ocular trauma, although visual potential for these patients is still limited.

Choroidal neovascularization in black patients.

OBJECTIVE: To characterize choroidal neovascularization (CNV) in black patients examined at a retinal disease referral center. DESIGN: Retrospective review of the medical records of all patients diagnosed as having CNV to identify black patients with CNV. SETTING: Single tertiary retinal referral center that included four ophthalmologists. PATIENTS: All patients diagnosed as having CNV between April 1990 and October 1992. MAIN OUTCOME MEASURES: Prevalence, demographic information, fundus photographic and fluorescein angiographic characteristics, natural history, and response to laser photocoagulation of CNV in black patients. RESULTS: Black patients comprise 15% of all patients seen at this center. Of 1725 patients identified as having CNV who were seen at the center during a 2.5-year period, only 25 were black (1.4%). In these patients, CNV was associated with a variety of retinal diseases, the most frequent being age-related macular degeneration. The average age of the study group was 54 years, women outnumbered men 2:1, and 13 of the patients developed bilateral lesions. Twelve of the 38 lesions were extrafoveal on presentation, and five of these were peripapillary. In the laser-treated eyes, recurrence of CNV was frequent and associated with visual loss. CONCLUSIONS: Choroidal neovascularization seems to be rare in blacks among a retinal disease referral center population. The overall presentation, natural history, and response to laser treatment seems to be similar to that of white patients. No feature of CNV in black patients was identified that would suggest that results of randomized clinical trials of laser photocoagulation for CNV are not valid for these patients.