Mark S. Blumenkranz

Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Macular Edema Due to Retinal Vein Occlusion

OBJECTIVE To evaluate the safety and efficacy of dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, CA) compared with sham in eyes with vision loss due to macular edema (ME) associated with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). DESIGN Two identical, multicenter, masked, randomized, 6-month, sham-controlled clinical trials (each of which included patients with BRVO and patients with CRVO). PARTICIPANTS A total of 1267 patients with vision loss due to ME associated with BRVO or CRVO. INTERVENTION A single treatment with DEX implant 0.7 mg (n = 427), DEX implant 0.35 mg (n = 414), or sham (n = 426). MAIN OUTCOME MEASURES The primary outcome measure for the pooled data from the 2 studies was time to achieve a > or =15-letter improvement in best-corrected visual acuity (BCVA). Secondary end points included BCVA, central retinal thickness, and safety. RESULTS After a single administration, the time to achieve a > or =15-letter improvement in BCVA was significantly less in both DEX implant groups compared with sham (P<0.001). The percentage of eyes with a > or =15-letter improvement in BCVA was significantly higher in both DEX implant groups compared with sham at days 30 to 90 (P<0.001). The percentage of eyes with a > or =15-letter loss in BCVA was significantly lower in the DEX implant 0.7-mg group compared with sham at all follow-up visits (P< or =0.036). Improvement in mean BCVA was greater in both DEX implant groups compared with sham at all follow-up visits (P< or =0.006). Improvements in BCVA with DEX implant were seen in patients with BRVO and patients with CRVO, although the patterns of response differed. The percentage of DEX implant-treated eyes with intraocular pressure (IOP) of > or =25 mmHg peaked at 16% at day 60 (both doses) and was not different from sham by day 180. There was no significant between-group difference in the occurrence of cataract or cataract surgery. CONCLUSIONS Dexamethasone intravitreal implant can both reduce the risk of vision loss and improve the speed and incidence of visual improvement in eyes with ME secondary to BRVO or CRVO and may be a useful therapeutic option for eyes with these conditions.

Vitrectomy for Diabetic Macular Traction and Edema Associated with Posterior Hyaloidal Traction

Pars plana vitrectomy with separation of the posterior hyaloid was performed in 10 eyes with diabetic macular edema and traction associated with a thickened and taut premacular posterior hyaloid. Nine of the 10 eyes had previous macular photocoagulation. Preoperative fluorescein angiography showed a deep and diffuse pattern of leakage in the macula. Intraoperatively, the attached and thickened posterior hyaloid was lifted and separated from the retina. Postoperatively, vision improved in nine eyes. The macular traction and edema resolved in eight eyes and decreased in two. Complications included a vitreous hemorrhage, a rhegmatogenous retinal detachment, cataract formation, and a mild epimacular membrane, each occurring in one eye. Vitreous surgery can improve the visual prognosis of some eyes with diabetic macular traction and edema associated with a thickened and taut posterior hyaloid.

Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results

OBJECTIVE To evaluate the safety and efficacy of 1 or 2 treatments with dexamethasone intravitreal implant (DEX implant) over 12 months in eyes with macular edema owing to branch or central retinal vein occlusion (BRVO or CRVO). DESIGN Two identical, multicenter, prospective studies included a randomized, 6-month, double-masked, sham-controlled phase followed by a 6-month open-label extension. PARTICIPANTS We included 1256 patients with vision loss owing to macular edema associated with BRVO or CRVO. METHODS At baseline, patients received DEX implant 0.7 mg (n = 421), DEX implant 0.35 mg (n = 412), or sham (n = 423) in the study eye. At day 180, patients could receive DEX implant 0.7 mg if best-corrected visual acuity (BCVA) was <84 letters or retinal thickness was >250 μm. MAIN OUTCOME MEASURES The primary outcome for the open-label extension was safety; BCVA was also evaluated. RESULTS At day 180, 997 patients received open-label DEX implant. Except for cataract, the incidence of ocular adverse events was similar in patients who received their first or second DEX implant. Over 12 months, cataract progression occurred in 90 of 302 phakic eyes (29.8%) that received 2 DEX implant 0.7 mg injections versus 5 of 88 sham-treated phakic eyes (5.7%); cataract surgery was performed in 4 of 302 (1.3%) and 1 of 88 (1.1%) eyes, respectively. In the group receiving two 0.7-mg DEX implants (n = 341), a ≥ 10-mmHg intraocular pressure (IOP) increase from baseline was observed in (12.6% after the first treatment, and 15.4% after the second). The IOP increases were usually transient and controlled with medication or observation; an additional 10.3% of patients initiated IOP-lowering medications after the second treatment. A ≥ 15-letter improvement in BCVA from baseline was achieved by 30% and 32% of patients 60 days after the first and second DEX implant, respectively. CONCLUSIONS Among patients with macular edema owing to BRVO or CRVO, single and repeated treatment with DEX implant had a favorable safety profile over 12 months. In patients who qualified for and received 2 DEX implant injections, the efficacy and safety of the 2 implants were similar with the exception of cataract progression. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-Year results of a randomized clinical trial - VIP report no. 3

PURPOSE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: A comparison with ophthalmoscopy and standardized mydriatic color photography

PURPOSE To evaluate single-field digital monochromatic nonmydriatic fundus photography as an adjunct in the screening of diabetic retinopathy. DESIGN Prospective, comparative, observational case series. METHODS Patients with type I and type II diabetes mellitus (n = 197) were sequentially evaluated by three different techniques: single-field digital monochromatic nonmydriatic photography; dilated ophthalmoscopy by an ophthalmologist; and seven Early Treatment Diabetic Retinopathy Study (ETDRS) standardized 35-mm color stereoscopic mydriatic images. The seven stereoscopic color photographs served as the reference standard and were compared with either ophthalmoscopy or a single digital photograph transmitted electronically to a reading site. Levels of agreement were determined by kappa analyses. The sensitivity and specificity of the three methods were compared based on a threshold for referral to further ophthalmologic evaluation (ETDRS level > or =35). RESULTS There was highly significant agreement (kappa = 0.97, P =.0001) between the degree of retinopathy detected by a single nonmydriatic monochromatic digital photograph and that seen in seven standard 35-mm color stereoscopic mydriatic fields. The sensitivity of digital photography compared with color photography was 78%, with a specificity of 86%. Agreement was poor (kappa = 0.40, P =.0001) between mydriatic ophthalmoscopy and the seven-field standard 35-mm color photographs. Sensitivity of ophthalmoscopy compared with color photography was 34%, with a specificity of 100%. CONCLUSION A single nonmydriatic monochromatic wide-field digital photograph of the disk and macula was more sensitive for diabetic retinopathy screening than mydriatic ophthalmoscopy, the currently accepted screening method. When adjudicated by standard seven-field color photographs, the higher sensitivity of digital photography primarily reflected the reduced sensitivity of ophthalmoscopy in detecting early retinopathy.

Femtosecond laser capsulotomy.

PURPOSE: To evaluate a femtosecond laser system to create the capsulotomy. SETTING: Porcine and cadaver eye studies were performed at OptiMedica Corp., Santa Clara, California, USA; the human trial was performed at the Centro Laser, Santo Domingo, Dominican Republic. DESIGN: Experimental and clinical study. METHODS: Capsulotomies performed by an optical coherence tomography–guided femtosecond laser were evaluated in porcine and human cadaver eyes. Subsequently, the procedure was performed in 39 patients as part of a prospective randomized study of femtosecond laser‐assisted cataract surgery. The accuracy of the capsulotomy size, shape, and centration were quantified and capsulotomy strength was assessed in the porcine eyes. RESULTS: Laser‐created capsulotomies were significantly more precise in size and shape than manually created capsulorhexes. In the patient eyes, the deviation from the intended diameter of the resected capsule disk was 29 μm ± 26 (SD) for the laser technique and 337 ± 258 μm for the manual technique. The mean deviation from circularity was 6% and 20%, respectively. The center of the laser capsulotomies was within 77 ± 47 μm of the intended position. All capsulotomies were complete, with no radial nicks or tears. The strength of laser capsulotomies (porcine subgroup) decreased with increasing pulse energy: 152 ± 21 mN for 3 μJ, 121 ± 16 mN for 6 μJ, and 113 ± 23 mN for 10 μJ. The strength of the manual capsulorhexes was 65 ± 21 mN. CONCLUSION: The femtosecond laser produced capsulotomies that were more precise, accurate, reproducible, and stronger than those created with the conventional manual technique. Financial Disclosure: The authors have equity interest in OptiMedica Corp., which manufactures the femtosecond laser cataract system.

Fluorouracil for the Treatment of Massive Periretinal Proliferation

A single intravitreal injection of fluorouracil was effective in the treatment of an experimental model of massive periretinal proliferation. When given with an intravitreal injection of 250,000 heterologous fibroblasts, fluorouracil decreased the rate of tractional retinal detachment from 36.8% in controls (seven of 19 eyes) to 5.2% in treated animals (one of 19 eyes) at one week, and from 73.6% in controls (14 of 19 eyes) to 31.5% in treated animals (six of 19 eyes) after four weeks (P less than .05). Intraocular neovascularization was reduced from 52.6% in controls (ten of 19 eyes) to 5.2% in treated animals (one of 19 eyes) after one week and 36.8% in controls (seven of 19 eyes) to 5.2% in treated animals (one of 19 eyes) after four weeks. When supplemented by repeated 10-mg subconjunctival injections of fluorouracil, or in combination with intravitreally administered indomethacin, this effect appeared to be enhanced. Intravitreal and subconjunctival injections of fluorouracil were well tolerated and may prove to be of significant value in the treatment of human disease.

Risk Factors in Age-related Maculopathy Complicated by Choroidal Neovascularization

We evaluated previously reported and hypothesized risk factors for the development of age-related maculopathy (ARM) in a case-control study. We compared 26 patients with documented disciform scarring or choroidal neovascularization with 23 age- and sex-matched controls. Systolic and diastolic blood pressure, smoking history, glucose, lipoprotein profiles, and serum levels of vitamins A, C, and E did not differ significantly between the two groups. Statistically significant associations (P less than 0.05) identified by univariate analysis include degree of dermal elastotic degeneration in sun-exposed and sun-protected skin, white blood count, increasing age and small posterior lenticular opacities. Using an interactive multivariate model, only extent of elastosis in sun protected dermis, age and white blood count were predictive (Mult R = 0.652, P less than .001). Our data support the concept of a multifactorial etiology of ARM but suggest that generalized increased susceptibility of elastic fibers to photic or other degenerative stimuli is a new and important risk factor for choroidal neovascularization.

Varicella Zoster Virus is a Cause of the Acute Retinal Necrosis Syndrome

We studied two blind eyes enucleated during the active phase of the acute retinal necrosis syndrome. Both eyes showed similar histopathologic findings of necrotizing retinitis, retinal arteritis, and optic neuropathy. A virus morphologically consistent with a herpes group virus was found on electron microscopy and immunocytopathologic stains showed this virus to be varicella zoster in both cases. Varicella zoster virus was cultured from the vitreous of one of the eyes. We conclude that varicella zoster virus retinal infection is a cause of the acute retinal necrosis syndrome.

The Acute Retinal Necrosis Syndrome: Part 2: Histopathology and Etiology

The acute retinal necrosis syndrome is manifested by diffuse uveitis, vitritis, retinal vasculitis, and acute necrotizing retinitis (see Part 1). We studied the histopathology and electron microscopic findings of an eye enucleated from a 67-year-old man with typical acute retinal necrosis. Histology showed profound acute necrosis of the retina, retinal arteritis, and eosinophilic intranuclear inclusions in retinal cells. Electron microscopy demonstrated a herpes group virus in all layers of affected retina. The implications of these findings for antiviral and other treatments are discussed.