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To assess the effect of duration of macular edema (ME) on clinical outcomes after treatment with dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc, Irvine, CA) in patients with ME following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).Post hoc analysis of pooled data from 2 randomized, controlled trials.Patients with vision loss resulting from ME of 6 weeks' duration or more after BRVO or CRVO (n = 690).The relationship between ME duration at the time of first treatment and treatment outcomes was assessed using logistic regression. Other factors potentially associated with ME duration or patient outcomes were adjusted for in the analyses.The proportion of patients achieving at least 15 letters improvement in best-corrected visual acuity (BCVA) or at least 200-μm or more reduction in central retinal thickness 6 or 12 months after the first treatment with dexamethasone intravitreal implant 0.7 mg.In the 6-month analysis, each 1-month increase in ME duration was associated with a significantly lower likelihood of achieving a BCVA improvement of 15 letters or more (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.83-0.94; P0.001) or a CRT reduction of 200-μm or more (OR, 0.91; 95% CI, 0.86-0.97; P0.01) 6 months after treatment. In the 12-month analysis, increased ME duration was associated with a significantly lower likelihood of achieving BCVA improvement of 15 letters or more improvement in BCVA (OR, 0.85; 95% CI, 0.76-0.95; P0.01) 12 months after treatment; duration was not significantly associated with the likelihood of a CRT reduction of 200-μm or more at 12 months. In general, the effect of ME duration on outcomes was stronger and statistically significant in BRVO patients, but weaker and not statistically significant in CRVO patients.In eyes with retinal vein occlusion, longer ME duration at the time of first treatment with the dexamethasone intravitreal implant 0.7 mg was associated with a significantly lower likelihood of achieving clinically meaningful improvements in vision or CRT 6 or 12 months after treatment. This suggests that prompt treatment for retinal vein occlusion, particularly BRVO, may be associated with improved clinical outcomes.Proprietary or commercial disclosure may be found after the references.

Purpose To determine the association between complement factor H (CFH) polymorphism T1277C (tyrosine-402 → histidine-402) and phenotypic variations of age-related macular degeneration (AMD). Design Cross-sectional observational study. Participants Subjects with dry or wet AMD and a control population consisting of age-matched non-AMD subjects from 2 clinical facilities examined during the period January 1, 1999 through December 31, 2002. Methods Total DNA isolated from the leukocytes of 66 AMD subjects and 58 age-matched control subjects was studied. The CFH gene was amplified by polymerase chain reaction and analyzed by Nla III restriction fragment length analysis. Main Outcome Measures Incidence of CHF polymorphism with the occurrence of AMD. Results Among the AMD patients, 15 had dry and 51 had wet AMD. For the CFH gene, the T1277C variant showed the genotype distribution as CC, TC, and TT. There was a strong association between homozygous C and AMD compared with the control population (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.32–8.74; P = 0.0053). Furthermore, dry AMD had a stronger association (OR, 8.32; 95% CI, 2.30–30.11; P = 0.001) than wet AMD (OR, 2.49; 95% CI, 0.90–6.84; P = 0.039) compared with the control population. Homozygous T was more prevalent in the control subjects compared with AMD patients (OR, 5; 95% CI, 2.18–11.43; P = 0.00005). Conclusions Complement factor H polymorphism T1277C (tyrosine-402 → histidine-402) is strongly associated with both dry and wet AMD and points to a possible role for inflammation in the pathogenesis of AMD.

Purpose To compare the safety and efficacy of intravitreal versus posterior Sub–Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. Design Prospective, double-masked, randomized controlled trial. Participants Twelve patients (24 eyes) with bilateral diffuse diabetic macular edema. Intervention One eye of each patient was randomly assigned to receive a single 4-mg triamcinolone acetonide intravitreal injection and the fellow eye to receive a 40-mg triamcinolone acetonide posterior Sub–Tenon's capsule injection. Main Outcome Measures Changes in visual acuity and central macular thickness obtained using optical coherence tomography were measured during a 6-month follow-up. Potential treatment complications were monitored, including increases in intraocular pressure (IOP) and cataract progression. Results Both intravitreal and Sub–Tenon's capsule injections of triamcinolone acetonide resulted in significant but transient improvements in central macular thickness. The mean (±standard deviation [SD]) central macular thickness in eyes with intravitreal injection was significantly thinner than in the Sub–Tenon's capsule–injected eyes at 1 month (226.8±41.7 μ m and 431.5±165.8 μ m, respectively; P = 0.002) and 3 months (242.3 ± 93.9 μ m and 364.7±78.2 μ m, respectively; P = 0.005) after triamcinolone acetonide injection. The mean visual acuity (logarithm of the minimum angle of resolution) in the intravitreally injected eyes was significantly better than in the Sub–Tenon's capsule–injected eyes at 3 months post injection (0.832±0.293 and 1.107±0.339, respectively; P = 0.004). Intraocular pressure did not show any significant difference between the 2 forms of triamcinolone acetonide delivery at any follow-up visit, and no eyes had IOPs >25 mmHg. Conclusions The findings from our study neither advocate nor support the use of corticosteroids for the treatment of diabetic macular edema, but do imply that both intravitreal and Sub–Tenon's capsule injections of triamcinolone acetonide may be equally tolerated, with short-term performance clearly favoring the intravitreal (4 mg) more than the SBT capsule (40 mg) route for the anatomic and functional aspects of improvement tested in this investigation.

Purpose To describe the course of cytomegalovirus (CMV) retinitis in patients with AIDS in the era of highly active antiretroviral therapy (HAART). Design Multicenter, prospective, observational study. Participants Two hundred seventy-one patients with AIDS and CMV retinitis. Methods Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and fundus photographs. Photographs were evaluated for relapse of the retinitis (progression) by graders at a centralized reading center. Main outcome measure Retinitis progression (movement of the border of a CMV lesion ≥750 μm over a ≥750-μm front or occurrence of a new lesion one-quarter disc area or more in size). Results The overall rate of retinitis progression was 0.10/person-year (PY); among those with CD4+ T-cell counts of P Conclusions Compared with the rate of retinitis progression (∼3.0/PY) reported in the pre-HAART era, the rate of retinitis progression was reduced among patients in the HAART era, even among those with low CD4+ T-cell counts, who might be expected to behave most like patients from the pre-HAART era. However, these events also occurred among patients with high CD4+ T-cell counts and presumed immune recovery. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression. This article contains additional online-only material available at http://www.ophsource.com/periodicals/ophtha.

Purpose To compare vitrectomy procedures and visualization of posterior segment structures through multifocal silicone intraocular lenses (IOLs) with the same procedures through monofocal silicone IOLs in rabbit eyes. Design Experimental study. Participants Twelve eyes of six rabbits. Methods Each rabbit eye underwent phacoemulsification of the lens and posterior chamber implantation of a silicone multifocal or silicone monofocal IOL. The type of IOL (monofocal vs. multifocal) implanted in the first eye of each rabbit was randomly decided. The fellow eye then received the other IOL type. Vitrectomy procedures were performed through the IOLs by using a flat contact lens (part 1) or wide-angled contact lens (part 2) for visualization through fluid-filled (parts 1 and 2) and air-filled (part 2) eyes. Main outcome measures Image quality, stereopsis, and contrast were subjectively graded on a scale of 0 (none) to 4 (excellent) for each eye by each surgeon. Results In part 1, image quality averaged 4 for the monofocal IOL and 3.6 for the multifocal IOL. Stereopsis averaged 4 for the monofocal IOL and 4 for the multifocal IOL. Contrast averaged 4 for the monofocal IOL and 3.9 for the multifocal IOL. Vitrectomy with retinal surface maneuvers was successfully performed in both pigmented and nonpigmented rabbit eyes through both IOL types. In part 2, image quality, stereopsis, and contrast were rated as 4 for both multifocal and monofocal silicone IOLs. Air-fluid exchange was performed without difficulty. Image quality, stereopsis, and contrast were rated as 4 for air-filled eyes. Conclusions Visualization of posterior segment structures through multifocal silicone IOLs was sufficient for retinal surface maneuvers during vitrectomy procedures in both fluid-filled and air-filled rabbit eyes.

To present the safety and efficacy of intravitreal implants releasing 0.2 μg/day fluocinolone acetonide (FAc) in patients with chronic versus nonchronic diabetic macular edema (DME). To assess ocular characteristics, anatomic changes, and re-treatment and ancillary therapies that may explain the differential treatment effect seen with intravitreal implants releasing FAc 0.2 μg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk assessment for the FAc 0.2-μg/day and FAc 0.5-μg/day doses has been reported previously.Preplanned subgroup analysis of chronic (duration of diagnosis, ≥3 years) and nonchronic (duration of diagnosis,3 years) DME in patients from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials.Patients with persistent DME despite 1 or more macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc 0.2 μg/day (n = 375), or FAc 0.5 μg/day (n = 393).Patients received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on re-treatment criteria, additional masked study drug could be given after 1 year.Percentage of patients with improvement of 15 letters or more from baseline. Secondary outcomes included other parameters of visual function and foveal thickness.At month 36, the difference between FAc 0.2 μg/day and sham control in the percentage of patients who gained 15 letters or more was significantly greater in chronic DME patients (FAc 0.2 μg/day, 34.0% vs. sham, 13.4%; P0.001), compared with patients with nonchronic DME (FAc 0.2 μg/day, 22.3% vs. sham, 27.8%; P = 0.275). The greater response in patients with chronic DME was not associated with baseline ocular characteristics, changes in anatomic features, or differences in re-treatment or ancillary therapies. The ocular adverse event profile for FAc 0.2 μg/day was similar regardless of DME duration.This is the first published analysis correlating duration of diagnosis of DME with treatment effect. In patients with chronic DME, FAc 0.2 μg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy.

Purpose To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME). Design Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial. Participants Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled. Intervention Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed. Main Outcome Measures The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP). Results The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 ( P P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 ( P ≤0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 ( P ≤0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required. Conclusions There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Background: Full-thickness macular holes generally cause a significant reduction in visual acuity, due in part to a rim of surrounding neurosensory retinal detachment and retinal thickening. Recent studies have suggested that flattening of this narrow rim of neurosensory detachment can result in improved visual acuity. However, the ability to flatten the neurosensory detachment is limited using current surgical techniques. Methods: Transforming growth factor-β 2 (TGF-β 2 ) is a recently discovered potent stimulator of wound healing. The authors, therefore, performed a prospective randomized study of 60 patients to determine if the local application of TGF-β 2 to the edge of the macular hole can reproducibly induce flattening of the surrounding neurosensory detachment. The results of a study designed to determine the effect of a pars plana vitrectomy, fluid-gas exchange, and intravitreal instillation of TGF-β 2 in eyes with a fullthickness macular hole and reduced visual acuity are reported. Results: After treatment, visual acuity improved 2 lines or more in 5 of 11 eyes treated with 70 ng, in 4 of 12 eyes treated with 330 ng, and in 10 of 11 eyes treated with 1330 ng of TGF-β 2 . In some eyes, hyaluronic acid was added. In these cases, visual acuity improved 2 lines or more in 0 of 9 eyes treated with 70 ng TGF-β 2 , in 2 of 8 eyes treated with 330 ng, and in 4 of 9 eyes treated with 1330 ng. Conclusion: Logistic regression analysis demonstrated a statistically significant beneficial effect of TGF-β 2 on visual improvement ( P = 0.003).

Giant retinal tears complicated by proliferative vitreoretinopathy (PVR) pose one of the more complex problems in vitreoretinal surgery. The authors developed a technique using perfluoro-octane, a temporary vitreous substitute that is heavier than water, combined with vitrectomy, scleral buckling, fluid-gas exchange, and direct manipulation of the retina to treat these cases. Ten eyes with giant retinal tears and grade D-1 PVR or worse were treated. In all eyes, the retina was successfully reattached at the end of surgery. Nine of the ten retinas remained attached after 6 months of follow-up. Five eyes required a total of six reoperations for epiretinal membrane formation without retinal detachment. The one eye in which the retina did not remain reattached developed severe recurrent PVR and iris neovascularization. Visual acuity improved in 8 of 10 eyes. Final visual acuity was 20/400 or better in 8 of 10 eyes, and 20/80 or better in 4 eyes.

Purpose To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes. Design Retrospective chart review. Participants Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001. Methods Baseline for each patient was the date of the first implantation procedure performed during the study period by one of the facilities’ surgeons (index implant). Medical and ophthalmological data were collected at baseline and at specific time points after baseline. The dates on which additional implantation procedures were performed and the dates on which complications or vision loss were identified were also recorded. Relationships between potential risk factors and outcomes were studied by Kaplan–Meier analyses and Cox proportional hazards regression models. Main Outcome Measures Primary outcome measures included postoperative complications specifically related to or possibly related to ganciclovir implants. A secondary outcome measure was vision loss after implantation procedures. Results The charts of 174 patients (one study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4 months (range, 0–7 years). Complications specifically related to implants occurred throughout follow-up at a rate of 0.064 events per patient-year. Complications possibly related to implants occurred at an overall rate of 0.377 per patient-year, but seemed to be more common during the first 2 years after baseline. During the first 2 years of follow-up, retinal detachments occurred at a rate of 0.156 events per patient-year. The cumulative risk of vision loss (≥3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were associated with disease factors (size and activity of lesions), lack of highly active antiretroviral therapy (HAART), and lack of HAART-associated immune reconstitution, but not with surgical factors or implant-specific complications. Conclusions Complications specifically associated with ganciclovir implants can occur many years after implantation procedures, but the incidence of such complications is low. Continued vision loss is not attributable directly to complications of implants in most cases. This information will help in planning of treatment strategies for CMV retinitis in long-term survivors of human immunodeficiency virus disease.

To describe the course of cytomegalovirus (CMV) retinitis in patients with AIDS in the era of highly active antiretroviral therapy (HAART).Multicenter, prospective, observational study.Two hundred seventy-one patients with AIDS and CMV retinitis.Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and fundus photographs.Second (contralateral) eye involvement among patients with unilateral disease and retinal detachment (RD).The overall rate of second eye involvement among patients with unilateral CMV retinitis was 0.07 per person-year (PY); among those with CD4+ T-cell counts of50/microl it was 0.34/PY, compared with 0.02/PY among those with CD4+ T-cell counts ofor =200/microl (P0.0001). Risk factors for contralateral eye involvement included low CD4+ T-cell count and detectable CMV load. The overall rate of RD was 0.06/PY; among those with CD4+ T-cell counts of50/microl it was 0.30/PY, compared with 0.02/PY among those with CD4+ T-cell counts ofor =200/microl (P0.0001). Risk factors for RD included a low CD4+ T-cell count and larger area of CMV retinitis.Compared with the rates reported in the pre-HAART era of second eye involvement (approximately 0.40/PY) and RD (approximately 0.50/PY), the rates of these events were reduced among patients in the HAART era. However, among patients with CD4+ T-cell counts of50/microl, the rates were more similar to those from the pre-HAART era.

To describe the course of cytomegalovirus (CMV) retinitis in patients with AIDS in the era of highly active antiretroviral therapy (HAART).Multicenter, prospective, observational study.Two hundred seventy-one patients with AIDS and CMV retinitis.Follow-up every 3 months with medical history, ophthalmologic examination, laboratory testing, and fundus photographs. Photographs were evaluated for relapse of the retinitis (progression) by graders at a centralized reading center.Retinitis progression (movement of the border of a CMV lesionor =750 microm over aor =750-microm front or occurrence of a new lesion one-quarter disc area or more in size).The overall rate of retinitis progression was 0.10/person-year (PY); among those with CD4+ T-cell counts of50/microl, it was 0.58/PY, compared to 0.02/PY among those with CD4+ T-cell counts ofor =200/microl (P0.0001). In the multivariate analysis, significant risk factors for retinitis progression included a low CD4+ T-cell count, positive CMV load, longer time from AIDS diagnosis, and low Karnofsky score.Compared with the rate of retinitis progression (approximately 3.0/PY) reported in the pre-HAART era, the rate of retinitis progression was reduced among patients in the HAART era, even among those with low CD4+ T-cell counts, who might be expected to behave most like patients from the pre-HAART era. However, these events also occurred among patients with high CD4+ T-cell counts and presumed immune recovery. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression.

Purpose To present the safety and efficacy of intravitreal implants releasing 0.2 μg/day fluocinolone acetonide (FAc) in patients with chronic versus nonchronic diabetic macular edema (DME). To assess ocular characteristics, anatomic changes, and re-treatment and ancillary therapies that may explain the differential treatment effect seen with intravitreal implants releasing FAc 0.2 μg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk assessment for the FAc 0.2-μg/day and FAc 0.5-μg/day doses has been reported previously. Design Preplanned subgroup analysis of chronic (duration of diagnosis, ≥3 years) and nonchronic (duration of diagnosis, Participants Patients with persistent DME despite 1 or more macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc 0.2 μg/day (n = 375), or FAc 0.5 μg/day (n = 393). Methods Patients received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on re-treatment criteria, additional masked study drug could be given after 1 year. Main Outcome Measures Percentage of patients with improvement of 15 letters or more from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. Results At month 36, the difference between FAc 0.2 μg/day and sham control in the percentage of patients who gained 15 letters or more was significantly greater in chronic DME patients (FAc 0.2 μg/day, 34.0% vs. sham, 13.4%; P P = 0.275). The greater response in patients with chronic DME was not associated with baseline ocular characteristics, changes in anatomic features, or differences in re-treatment or ancillary therapies. The ocular adverse event profile for FAc 0.2 μg/day was similar regardless of DME duration. Conclusions This is the first published analysis correlating duration of diagnosis of DME with treatment effect. In patients with chronic DME, FAc 0.2 μg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy.

Purpose: The management of cytomegalovirus (CMV)-related rhegmatogenous retinal detachments in patients with acquired immune deficiency syndrome (AIDS) has been the subject of recent attention and controversy because of the high degree of variability in visual outcome, as well as significant differences in the reported incidence of profound postoperative optic atrophy. This study was designed to evaluate the various parameters affecting postoperative visual outcome, and to quantitate the degree of postoperative optic disc pallor. Methods: The results of 65 consecutive surgeries for CMV-related retinal detachments in 51 patients with AIDS were prospectively studied. Postoperative vision, survival, optic disc pallor, and retinitis extent were analyzed. Serial photographs of optic discs underwent masked evaluation. Results: Mean postoperative survival was 30 weeks (range, 2–146 weeks). Mean best postoperative visual acuity was 20/66 (range, 20/20-2/200) and mean final post-operative visual acuity was 20/100 (range, 20/25-no light perception). Analysis of visual outcome for eyes with no macular or papillo-macular retinitis showed a best postoperative visual acuity of 20/60 (range, 20/25-2/200) and mean final postoperative visual acuity of 20/80 (range, 20/25-no light perception). Postoperative vision was not affected by the presence of a preoperative macular detachment, with both groups (macula on or off detachments), achieving a best postoperative visual acuity of 20/60 in the absence of macular retinitis. Mild postoperative optic disc pallor was observed in 30% of surgical eyes at the final postoperative visit, and moderate pallor was noted in 13%. The mean degree of optic disc pallor was not different from the degree of optic disc pallor seen in fellow, nonsurgical eyes with CMV retinitis (surgical versus fellow nonsurgical eyes, 29% ± 23% versus 26% ± 30%; P = 0.64). Conclusion: In this largest reported series of reattachment surgery for CMV-related retinal detachments, patients are experiencing increased postoperative survival, good vision, and relative optic nerve health.