Donald J. D'Amico

Increased Vascular Endothelial Growth Factor Levels in the Vitreous of Eyes With Proliferative Diabetic Retinopathy

The vitreous levels of the angiogenic polypeptide vascular endothelial growth factor (also known as vascular permeability factor) were measured and compared in eyes with and without proliferative diabetic retinopathy. Undiluted vitreous samples from 20 eyes were collected at the time of vitrectomy, and vascular endothelial growth factor levels were determined by using a time-resolved immunofluorometric assay. Vitreous vascular endothelial growth factor levels were significantly higher in eyes with proliferative diabetic retinopathy than in eyes without proliferative diabetic retinopathy (P = .006; Wilcoxon Rank Sum Test). The median vitreous concentration in the eyes with proliferative diabetic retinopathy was 29.1 pM and exceeded the known concentration required for the maximal proliferation of vascular endothelial cells in vitro. These data are consistent with vascular endothelial growth factor serving as a physiologically relevant angiogenic factor in proliferative diabetic retinopathy.

Evolving guidelines for intravitreous injections.

Intravitreous (IVT) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene™) is currently approved by the Food and Drug Administration as an IVT injection, the number of approved IVT injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for IVT injection. The purpose of this document is to identify specific strategies for the delivery of IVT injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of IVT injection, additional clinical experience, and results of clinical trials.

Treatment of Cytomegalovirus Retinitis with 9-[2-Hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine

Cytomegalovirus infections can cause significant morbidity and mortality in immunosuppressed patients, and present antiviral agents have had little efficacy against these infections. We describe the use of an acyclic nucleoside 9-[2-hydroxy-1-(hydroxymethyl) ethoxy methyl]guanine (BW B759U), in the treatment of two patients with cytomegalovirus retinitis. The efficacy of this agent was evident, with healing of retinal lesions and resolution of viremia and viral shedding. BW B759U appears to be similar pharmacokinetically to intravenous acyclovir in terms of half-life, peak serum levels, and renal excretion.

Posterior Segment Complications after Vitrectomy for Macular Hole

PURPOSE The purpose of this study is to assess the rate of posterior segment complications after vitreous surgery for macular holes and to evaluate the effect of such complications on final visual outcome. METHODS The authors reviewed retrospectively all cases of vitreous surgery for macular holes performed between June 1990 and October 1993. Among 98 patients with a followup of 3 months or more, all patients with posterior segment complications during the postoperative course were identified. The rate of complications was compared with that seen after vitreous surgery for macular pucker performed by the same surgeons. RESULTS Posterior segment complications were noted in 23 (23%) of 98 patients. These included peripheral retinal breaks (3%), rhegmatogenous retinal detachment from a peripheral retinal break (14%), enlargement of the hole (2%), late reopening of the hole (2%), retinal pigment epithelium loss under the hole (1%), photic toxicity (1%), and endophthalmitis (1%). In 40% of these eyes, the final visual acuity was two lines or more below preoperative visual acuity. When compared with the macular pucker group, the rate of posterior segment complications, in particular the rate of peripheral retinal tears and detachments, was significantly higher (P < or = 0.05). CONCLUSIONS The authors conclude that visually significant posterior segment complications may occur after vitrectomy for macular hole, and the rate of these complications appears to be higher than expected.

Comparative Toxicity of Intravitreal Aminoglycoside Antibiotics

We compared the toxicity of the aminoglycoside antibiotics (tobramycin, amikacin, netilmicin, and kanamycin) by ophthalmoscopy, light and electron microscopy, and electro-retinography after intravitreal injection in rabbits in doses ranging from 100 to 3,000 micrograms. The earliest manifestations of toxicity were confined to the outer retina with each drug, with lamellar lysosomal inclusions in the retinal pigment epithelium as the earliest finding. However, the aminoglycosides displayed marked differences in the threshold dose required to produce toxic reactions, permitting the following ordering of toxicity: (most toxic) gentamicin greater than netilmicin = tobramycin greater than amikacin = kanamycin (least toxic).

Subretinal fibrosis after laser photocoagulation for diabetic macular edema.

Seven eyes had subretinal fibrosis after grid laser photocoagulation for diabetic macular edema. The fibrosis caused persistent loss in visual acuity, and in six of the seven eyes, was not associated with detectable laser-induced Bruchs membrane rupture or subretinal hemorrhage. Choroidal neovascularization was detected in only one patient, who was notably younger (27 years) than the median age of 70 years in this series. The median preoperative visual acuity was 20/80 (range, 20/40 to 20/400); the median postoperative visual acuity was 20/400 (range, 20/80 to counting fingers). The subretinal fibrosis was detected at a median of three months (range, 14 days to 4 1/2 months) after laser therapy. In one of five bilaterally treated patients (20%), subretinal fibrosis developed in both eyes. Subretinal fibrosis may be caused by undetected choroidal neovascularization or by excessive proliferation after stimulation of an aged retinal pigment epithelium. Subretinal fibrosis may be a potential cause of loss in visual acuity after laser treatment for diabetic macular edema.

Endogenous Bacterial Endophthalmitis

PURPOSE The purpose of this study is to report the predisposing factors, timing of symptoms, timing of diagnosis, causative organisms, source of infection, and visual outcome in cases of endogenous bacterial endophthalmitis. METHODS The records of 28 patients with endogenous bacterial endophthalmitis who presented to our combined ophthalmology and medicine services over a 10-year period were reviewed. RESULTS Ninety percent of the patients had prior medical conditions, including diabetes mellitus, gastrointestinal disorders, hypertension, cardiac disorders, and malignancy. Acute ocular symptoms were the most common reasons why the patient went to the physician (usually an ophthalmologist) rather than systemic symptoms. A correct initial diagnosis was made in 50% of patients, with a delay in diagnosis of 4 days or more in 29% of patients. Organisms were identified in 27 of the 28 patients (96% identification rate), two thirds of which were gram-positive organisms. Streptococcal species were the most common group (32% of patients), although the single most common organism was Staphylococcus aureus (25% of patients). Sources of infection were identified in 93% of patients, with endocarditis and the gastrointestinal tract being the most common. In the majority of patients, visual outcome was poor. However, six eyes that received intravenous and intravitreal antibiotics, as well as therapeutic vitrectomy, achieved visual acuities of 20/50 or better. CONCLUSION These results provide a further understanding of the manner of presentation, organisms involved, and sources of infection in endogenous bacterial endophthalmitis. They also suggest that improved outcome may be associated with early initiation of combined medical and surgical treatment.

Retinal toxicity of intravitreal triamcinolone acetonide: a morphological study.

Purpose: To evaluate the morphologic effects of intravitreal triamcinolone acetonide (TA) on rabbit retina. Methods: Intravitreal injections of 0.5 mg, 1 mg, 4 mg, 8 mg, and 20 mg of TA (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) in 0.1 mL were given to pigmented rabbits. For control, 0.1 mL of TA vehicle and saline were injected. Animals were killed on day 14, and retinas were analyzed by light as well as electron microscopy. Results: No ophthalmoscopic change was found. Eyes injected with 0.5 mg and 1 mg of TA did not have morphologic abnormality. Eyes injected with 4 mg, 8 mg, and 20 mg showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes injected with 20 mg showed more extensive damage and increased pigment granules in the retinal pigment epithelium cells with large oil droplets in the cytoplasm. Electron microscopy also showed loss of photoreceptor/retinal pigment epithelium interdigitations. Eyes injected with vehicle or saline did not show morphologic changes. Conclusion: Single intravitreal injection of 0.5 mg or 1 mg of TA did not produce morphologic retinal changes in pigmented rabbits. However, injections of 4 mg, 8 mg, and 20 mg of TA produced outer retina toxic effects. These findings suggest that long-term retinal toxicity studies should be carried out, using single and repeated injections before this therapy becomes more widely used.

Primary Retinal Detachment

A 57-year old man noted flashing lights in his right eye, followed two days later by a cluster of dark floaters that mildly interfered with his vision. He initially ignored these symptoms, but over the course of the next week, he noted a progressive loss of the nasal visual field in that eye, beginning inferiorly and spreading superiorly, with an eventual striking loss of central acuity that prompted him to seek ophthalmologic evaluation. Examination of the fundus with the pupil dilated showed a retinal detachment involving the temporal retina, including the macula, with peripheral retinal tears at the 10:30 and 11:30 positions. How should his case be managed?

Cataract surgery as a risk factor for retinal detachment in very highly myopic eyes

PURPOSE To evaluate the incidence of retinal detachment (RD) after cataract surgery performed by phacoemulsification in very highly myopic eyes. DESIGN Retrospective, paired-eye, case-control trial. PARTICIPANTS AND INTERVENTION We assessed the development of RD in 930 eyes from 930 subjects (mean age = 62.5 +/- 8.5 years) affected by very high myopia (between -15 and -30 diopters) undergoing cataract surgery after uncomplicated phacoemulsification (cataract-subjected [CS] eyes). Fellow eyes served as controls. Follow-up was 36 months. MAIN OUTCOME MEASURE Detachment of the retina. RESULTS Retinal detachment was observed in 8.0% of CS eyes compared with 1.2% of control eyes (P<0.01, chi-square test). In CS eyes, posterior RD was most common (52.7% of eyes with RD). In control eyes, peripheral detachments with or without macular involvement were most common (47.3% of eyes with RD). CONCLUSION Cataract surgery, despite the use of a safe technique such as phacoemulsification, increases the risk of RD development in very highly myopic eyes.