Gholam A. Peyman

Photocoagulation Treatment of Proliferative Diabetic Retinopathy: The Second Report of Diabetic Retinopathy Study Findings

Data from the Diabetic Retinopathy Study (DRS) show that photocoagulad inhibited the progression of retinopathy. These beneficial effects were noted to some degree in all those stages of diabetic retinopathy which were included in the Study. Some deleterious effects of treatment were also found, including losses of visual acuity and constriction of peripheral visual field. The risk of these harmful effects was considered acceptable in eyes with retinopathy in the moderate or severe retinopathy in the moderate or severe proliferative stage when the risk of severe visual loss without treatment was great. In early proliferative or severe nonproliferative retinopathy, when the risk of severe visual loss without treatment was less, the risks of harmful treatment effects assumed greater importance. In these earlier stages, DRS findings have not led to a clear choice between prompt treatment and deferral of treatment unless and until progression to a more severe stage occurs.

Testing intravitreal toxicity of bevacizumab (Avastin).

Purpose: To evaluate the retinal toxicity of varying doses of bevacizumab when injected intravitreally in rabbits. Bevacizumab has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer. Materials and Methods: Twelve New Zealand albino rabbits were used for this study and divided into four groups. Four concentrations of bevacizumab were prepared: 500 &mgr;g/0.1 mL, 1.0 mg/0.1 mL, 2.5 mg/0.1 mL, and 5.0 mg/0.2 mL. Each concentration was injected intravitreally in one eye of each of three rabbits; 0.1 mL volume of sterile balanced saline solution was injected into the contralateral eyes. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, or toxicity. A baseline electroretinogram (ERG) was performed before the drug treatment and at day 14 before the animals were killed. The enucleated eyes were prepared for histologic evaluation of retinal toxicity. Results: Histologic and ERG results in all groups showed no retinal toxicity. However, some inflammatory cells were found in the vitreous at the 5–mg dose. Conclusions: Intravitreal bevacizumab did not appear toxic to the retina in albino rabbits at a concentration of 2.5 mg. Intravitreally injected bevacizumab should be evaluated for efficacy in choroidal neovascularization and macular edema.

A Technique for Retinal Pigment Epithelium Transplantation for Age-Related Macular Degeneration Secondary to Extensive Subfoveal Scarring

We describe the surgical excision of submacular scar in end-stage age-related macular degeneration and transplantation of autologous and homologous retinal pigment epithelial (RPE) cells. The technique involves the preparation of a large retinal flap encompassing the macula and the arcades, removal of the submacular scar, and replacement of the RPE cells, using either an autologous pedicle graft or homologous RPE cells and Bruchs membrane. Fourteen months following the procedure, visual acuity in a patient with a pedicle graft had improved from counts fingers to 20/400 and the patient fixated over the transplanted RPE cells. After 10 months, a homologous graft in a second patient had become encapsulated with a fine subretinal membrane without neovascular tissue; visual acuity had not improved. No intraoperative or postoperative complications resulting from the surgery occurred in either patient.

Intravitreal triamcinolone acetonide for refractory chronic pseudophakic cystoid macular edema.

Purpose: To determine the safety and efficacy of intravitreal triamcinolone acetonide (TAAC) injections in patients with refractory cystoid macular edema (CME) after cataract extraction. Setting: LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. Methods: In this nonrandomized retrospective case review, 8 eyes of 8 patients with a history of pseudophakic CME recalcitrant to current standard treatment modalities were enrolled. The mean duration of the CME was 20 months. The patients received intravitreal injections of 1 mg of TAAC and were followed for a mean of 8 months. The main outcome measures included visual acuity, the presence of CME on biomicroscopic examination, angiographic evidence of perifoveal leakage, intraocular pressure (IOP), and complications related to treatment. Results: The visual acuity increased in all patients. The magnitude of improvement was mainly restricted by underlying macular pathology and correlated well with the level of visual acuity at entry into the study. Angiographic improvement occurred in all patients. Temporary increases in IOP were easily controlled with topical medications. No other adverse effects could be attributed to this technique. Repeated injections were required. Conclusions: Intravitreal administration of TAAC was safe and effective in recalcitrant cases of pseudophakic CME with a beneficial effect on the macular edema and visual acuity. A prospective randomized study is needed to determine with accuracy the efficacy, safety, and exact timing of this technique and possibly to recognize subtypes with a more favorable response. Repeated injections were required in all eyes. The development of a sustained‐release intravitreal drug‐delivery system would be beneficial.

Intravitreal injection of therapeutic agents.

Background: Intravitreal injection (IVI) with administration of various pharmacological agents is a mainstay of treatment in ophthalmology for endopthalmitis, viral retinitis, age-related macular degeneration, cystoid macular edema, diabetic retinopathy, uveitis, vascular occlusions, and retinal detachment. The indications and therapeutic agents are reviewed in this study. Methods: A search of the English, German, and Spanish language MEDLINE database was conducted. A total of 654 references spanning the period through early 2008 were individually evaluated. Results: The advantage of the IVI technique is the ability to maximize intraocular levels of medications and to avoid the toxicities associated with systemic treatment. Intravitreal injection has been used to deliver several types of pharmacological agents into the vitreous cavity: antiinfective and antiinflammatory medications, immunomodulators, anticancer agents, gas, antivascular endothelial growth factor, and several others. The goal of this review is to provide a detailed description of the properties of numerous therapeutic agents that can be delivered through IVI, potential complications of the technique, and recommendations to avoid side effects. Conclusion: The IVI technique is a valuable tool that can be tailored to the disease process of interest based on the pharmacological agent selected. This review provides the reader with a comprehensive summary of the IVI technique and its multitude of uses.

Intravitreal administration of antibiotic in the treatment of bacterial endophthalmitis. III. Consensus

Five years ago, we established the Viewpoints section on the premise that written constructive expression of differences of opinion about ophthalmic problems would increase the level of understanding in the profession. Since we thought that neither eloquence of expression nor vigor of debate would resolve the questions, we avoided a response-rebuttal format and simply asked each author to express his or her point of view along with the evidence supporting it, without seeing the others manuscript. Rather than rigidly cementing opinions, we hoped this approach would maintain maleable minds in the search for solutions to perplexing problems. In the inaugural Viewpoints section, Baum and Peyman discussed periocular versus intravitreal administration of antibiotics in the treatment of bacterial endophthalmitis (Antibiotic administration in the treatment of bacterial endophthalmitis. I. Baum JL: Periocular injections. II. Peyman GA: Intravitreal injections. Surv Ophthalmol 21:332-346, 1977). Now, in a novel format, the authors reappraise the subject and come to a consensus that minimizes the therapeutic quandary engendered by the original articles. While acknowledging that intravitreal administration of antibiotic is the preferred route for the treatment of bacterial endophthalmitis, the authors emphasize the lack of controlled and randomized clinical trials in this area. Their practical recommendations will assist the ophthalmologist who tries to forestall the devastation of bacterial endophthalmitis.

INTRAVITREAL BEVACIZUMAB (AVASTIN) INJECTION ALONE OR COMBINED WITH TRIAMCINOLONE VERSUS MACULAR PHOTOCOAGULATION AS PRIMARY TREATMENT OF DIABETIC MACULAR EDEMA

Purpose: To report the efficacy of a single intravitreal bevacizumab injection alone or in combination with intravitreal triamcinolone acetonide versus macular laser photocoagulation (MPC) as primary treatment of diabetic macular edema (DME). Methods: In this randomized, three-arm clinical trial, 103 eyes of 97 patients with clinically significant DME and no previous treatment were enrolled. The eyes were randomly assigned to one of three study arms: the intravitreal bevacizumab (IVB) group, patients who received 1.25 mg of intravitreal bevacizumab (37 eyes); the IVB/IVT group, patients who received 1.25 mg of intravitreal bevacizumab and 2 mg of intravitreal triamcinolone (33 eyes); and the MPC group, patients who underwent focal or modified grid laser (33 eyes). Primary outcome measure was change in visual acuity. Results: Visual acuity changes ± SD at 12 weeks were −0.22 ± 0.23, −0.13 ± 0.31, and + 0.08 ± 0.31 logarithm of the minimal angle of resolution in the IVB, IVB/IVT, and MPC groups, respectively. The marginal regression model based on generalized estimating equation analysis demonstrated that the visual acuity changes in the groups were statistically significant at both 6 weeks (P < 0.0001) and 12 weeks (P = 0.024). The significant treatment effect was demonstrated at both 6 weeks and 12 weeks in the IVB group and only at 6 weeks in the IVB/IVT group. Significant central macular thickness (CMT) reduction was observed in eyes in the IVB and IVB/IVT groups only up to 6 weeks; however, CMT changes were not significant in the groups. Conclusion: Up to 12 weeks, intravitreal bevacizumab treatment of patients with DME yielded better visual outcome than laser photocoagulation, although it was not associated with a significant decrease in CMT. No further beneficial effect of intravitreal triamcinolone could be demonstrated. Further clinical trials with longer follow-up are required to evaluate the long-term visual outcomes and complication profiles after primary treatment with such medications.

Prophylaxis of Pseudophakic Cystoid Macular Edema with Topical Indomethacin

A prospective double-masked study of 500 patients was performed to assess the effect of topical indomethacin on the angiographic incidence of cystoid macular edema (CME) in patients undergoing intraocular lens implant surgery. All patients received either topical indomethacin or placebo before surgery and for nine months after surgery. All patients underwent planned extracapsular extraction (PEC) or posterior chamber phacoemulsification (PC-KPE). Implantation of a posterior chamber lens and a primary capsulotomy were performed in all cases. All cases received postoperative topical corticosteroids. Of the 500 cases, 390 (78%) underwent fluorescein angiography; most were performed between 2 1/2 and 5 months after surgery. The incidence of angiographically confirmed CME was significantly higher in the placebo-treated patients as compared to those treated with indomethacin (18.5% vs 9.6%; P = 0.04). Patients 60 years of age or older had a significantly higher incidence of CME than younger individuals (15% vs. 3.4%; P = 0.03). When corrected for the effects of drug regimen and age, by means of multiple logistic regression, there was no significant correlation between procedure (PEC vs. PC-KPE) and CME rate (P = 0.62). There was no significant difference in postoperative visual acuity between the indomethacin- and placebo-treated patients (P = 0.65).

Prevention and Management of Traumatic Endophthalmitis

Twelve cases of traumatic culture-proven endophthalmitis were treated with intraocular antibiotics or in combination with vitrectomy. In 11 cases, the eyes were saved and in 10 the visual acuity was equal to or better than 20/200.

Delivery systems for intraocular routes

Abstract Intravitreal drug delivery has been developed to treat posterior segment diseases because the blood-ocular barrier prevents treatment by topical, systemic, or subconjunctival routes from attaining therapeutic levels in the vitreous. Endophthalmitis, uveitis, proliferative vitreoretinopathy, and viral retinitis are treated by intravitreal injection. Efforts to sustain drug delivery have included encapsulation of drugs in liposomes (made of lipids) or microspheres (made of polymers). In many instances the drugs toxicity to the retina was reduced and the clearance time was slowed. However, these methods cause clouding of the vitreous and can prolong drug delivery for only one month. Implantable devices have been used, such as an osmotic minipump, a drug pellet coated with polyvinyl alcohol and ethylene vinyl acetate, and polysulfone capillary fiber. Biodegradable devices are under investigation, including a drug matrix and a porous reservoir system, both made of polymers; these devices would not require surgical removal.