PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY: Should Baseline Characteristics Affect Choice of Treatment?

PURPOSE: Among eyes with proliferative diabetic retinopathy, identify whether baseline characteristics impact the benefit of ranibizumab over panretinal photocoagulation (PRP) in DRCR.net Protocol S. METHODS: Participants had proliferative diabetic retinopathy, visual acuity of 20/320 or better, and no previous PRP. Eyes were randomized to PRP or intravitreous 0.5-mg ranibizumab. RESULTS: Ranibizumab was superior to PRP for change in visual acuity and development of vision-impairing central-involved diabetic macular edema over 2 years (P < 0.001). Among 25 characteristics, there were none in which participants assigned to PRP had superior outcomes relative to ranibizumab-assigned participants. The relative benefit of ranibizumab over PRP for change in visual acuity seemed greater in participants with higher mean arterial pressure (P = 0.03), without previous focal/grid laser (P = 0.03), with neovascularization of the disk and elsewhere on clinical examination (P = 0.04), and with more advanced proliferative diabetic retinopathy on photographs (P = 0.02). For development of vision-impairing central-involved diabetic macular edema, the relative benefit of ranibizumab over PRP seemed greater among nonwhite participants (P = 0.01) and those with higher mean arterial pressure (P = 0.01). CONCLUSION: There were no characteristics identified in which outcomes were superior with PRP compared with ranibizumab. These exploratory analyses provide additional support that ranibizumab may be a reasonable alternative to PRP for proliferative diabetic retinopathy over a 2-year period.

Rationale and Application of the Protocol S Anti-Vascular Endothelial Growth Factor Algorithm for Proliferative Diabetic Retinopathy.

PURPOSE: To present the rationale, guidelines, and results of ranibizumab treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S. DESIGN: Post hoc analyses from a randomized clinical trial. PARTICIPANTS: Three hundred five participants (394 study eyes) having PDR without prior panretinal photocoagulation (PRP). METHODS: Intravitreous ranibizumab (0.5 mg) versus PRP for PDR. Ranbizumab-assigned eyes (n = 191) received monthly injections for 6 months unless resolution was achieved after 4 injections. After 6 months, injections could be deferred if neovascularization was stable over 3 consecutive visits (sustained stability). If neovascularization worsened, monthly treatment resumed. Panretinal photocoagulation could be initiated for failure or futility criteria. MAIN OUTCOME MEASURES: Neovascularization status through 2 years. RESULTS: At 1 month, 19% (35 of 188) of ranibizumab-assigned eyes showed complete neovascularization resolution and an additional 60% (113) showed improvement. At 6 months, 52% (80 of 153) showed neovascularization resolution, 3% (4) were improved, 37% (56) were stable, and 8% (13) had worsened since the last visit. Among eyes with versus without resolved neovascularization at 6 months, the median (interquartile range) number of injections between 6 months and 2 years was 4 (1-7; n = 73) versus 7 (4-11; n = 67; P < 0.001). Injections were deferred in 68 of 73 eyes (93%) meeting sustained stability at least once during the study; 62% (42 of 68) resumed injections within 16 weeks after deferral. At 2 years, 43% (66 of 154) showed neovascularization resolution, 5% (7) showed improvement, 23% (36) were stable, and 27% (42) had worsened since the last visit. Only 3 eyes met criteria for failure or futility through 2 years. CONCLUSIONS: The DRCR.net treatment algorithm for PDR can provide excellent clinical outcomes through 2 years for patients initiating anti-vascular endothelial growth factor (VEGF) therapy for PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR, treatment decisions should be guided by consideration of the relative advantages of each therapeutic method and anticipated patient compliance with follow-up and treatment recommendations.

Visual Acuity Outcomes in Diabetic Macular Edema With Fluocinolone Acetonide 0.2 µg/Day Versus Ranibizumab Plus Deferred Laser (DRCR Protocol I).

BACKGROUND AND OBJECTIVE: Visual outcomes of the FAME study (0.2 µg/day fluocinolone acetonide [FAc]) and Protocol I (0.5 mg ranibizumab plus deferred laser) were compared using the area under the curve (AUC) analysis method. PATIENTS AND METHODS: Best-corrected visual acuity (BCVA) data collected during a period of 3 years of follow-up for patients enrolled in FAME or Protocol I were used to calculate AUC of the change in BCVA over a time curve. RESULTS: In the overall population, there was a greater treatment effect for ranibizumab plus deferred laser compared with FAc. However, for subgroups of pseudophakic eyes, eyes with chronic diabetic macular edema (DME), and pseudophakic eyes with chronic DME, ranibizumab plus deferred laser and FAc were not found to be significantly different. The ranibizumab group received a median of 14 injections during a 36-month period compared with a mean of 1.3 injections in the FAc group. CONCLUSION: In pseudophakic and chronic DME subgroups, FAc was comparable to ranibizumab plus deferred laser with fewer injections. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:698-706.].

Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Importance: Ranibizumab is a viable treatment option for eyes with proliferative diabetic retinopathy (PDR) through 2 years. However, longer-term results are needed. Objective: To evaluate efficacy and safety of 0.5-mg intravitreous ranibizumab vs panretinal photocoagulation (PRP) over 5 years for PDR. Design, Setting, and Participants: Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial evaluated 394 study eyes with PDR enrolled February through December 2012. Analysis began in January 2018. Interventions: Eyes were randomly assigned to receive intravitreous ranibizumab (n = 191) or PRP (n = 203). Frequency of ranibizumab was based on a protocol-specified retreatment algorithm. Diabetic macular edema could be managed with ranibizumab in either group. Main Outcomes and Measures: Mean change in visual acuity (intention-to-treat analysis) was the main outcome. Secondary outcomes included peripheral visual field loss, development of vision-impairing diabetic macular edema, and ocular and systemic safety. Results: The 5-year visit was completed by 184 of 277 participants (66% excluding deaths). Of 305 enrolled participants, the mean (SD) age was 52 (12) years, 135 (44%) were women, and 160 (52%) were white. For the ranibizumab and PRP groups, the mean (SD) number of injections over 5 years was 19.2 (10.9) and 5.4 (7.9), respectively; the mean (SD) change in visual acuity letter score was 3.1 (14.3) and 3.0 (10.5) letters, respectively (adjusted difference, 0.6; 95% CI, -2.3 to 3.5; P = .68); the mean visual acuity was 20/25 (approximate Snellen equivalent) in both groups at 5 years. The mean (SD) change in cumulative visual field total point score was -330 (645) vs -527 (635) dB in the ranibizumab (n = 41) and PRP (n = 38) groups, respectively (adjusted difference, 208 dB; 95% CI, 9-408). Vision-impairing diabetic macular edema developed in 27 and 53 eyes in the ranibizumab and PRP groups, respectively (cumulative probabilities: 22% vs 38%; hazard ratio, 0.4; 95% CI, 0.3-0.7). No statistically significant differences between groups in major systemic adverse event rates were identified. Conclusions and Relevance: Although loss to follow-up was relatively high, visual acuity in most study eyes that completed follow-up was very good at 5 years and was similar in both groups. Severe vision loss or serious PDR complications were uncommon with PRP or ranibizumab; however, the ranibizumab group had lower rates of developing vision-impairing diabetic macular edema and less visual field loss. Patient-specific factors, including anticipated visit compliance, cost, and frequency of visits, should be considered when choosing treatment for patients with PDR. These findings support either anti-vascular endothelial growth factor therapy or PRP as viable treatments for patients with PDR. Trial Registration: ClinicalTrials.gov Identifier: NCT01489189.

Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Factors Associated with Vision and Edema Outcomes.

PURPOSE: To identify baseline factors associated with change in visual acuity or development of vision-impairing central-involved diabetic macular edema (DME) over 2 years when treating proliferative diabetic retinopathy (PDR) with ranibizumab or panretinal photocoagulation (PRP). DESIGN: Post hoc analyses of randomized, multicenter clinical trial data. PARTICIPANTS: Eyes completing the 2-year visit (n = 328) or without vision-impairing central-involved DME at baseline (n = 302) in Diabetic Retinopathy Clinical Research Network Protocol S. METHODS: Intravitreous ranibizumab (0.5 mg/0.05 ml) or PRP. MAIN OUTCOME MEASURES: Change in visual acuity (area under the curve) and development of vision-impairing (20/32 or worse) central-involved DME over 2 years. RESULTS: After multivariable model selection with adjustment for baseline visual acuity and central subfield thickness, no factors were identified as associated with change in visual acuity or development of vision-impairing central-involved DME within the ranibizumab group. In the PRP group, worse change in visual acuity was more likely with higher hemoglobin A1c level (-0.6 letters per 1% increase; 95% confidence interval [CI], -1.2 to -0.1 letters; continuous P = 0.03), more severe diabetic retinopathy (difference between high-risk PDR or worse vs. moderate PDR or better, -2.8 letters [95% CI, -5.5 to -0.2 letters]; continuous P = 0.003), and higher mean arterial pressure (difference between ≥100 mmHg vs. <100 mmHg, -2.0 letters [95% CI, -4.6 to 0.5 letters]; continuous P = 0.009). Development of vision-impairing central-involved DME was more likely with higher hemoglobin A1c level (hazard ratio [HR] per 1% increase, 1.31 [95% CI, 1.13-1.52]; continuous P < 0.001), more severe diabetic retinopathy (HR for high-risk PDR or worse vs. moderate PDR or better, 1.46 [95% CI, 0.73-2.92]; continuous P = 0.03), and the presence of cystoid abnormalities within 500 µm of the macula center (HR, 2.90 [95% CI, 1.35-6.24]; P = 0.006). CONCLUSIONS: For eyes managed with PRP, higher hemoglobin A1c level and more severe diabetic retinopathy were associated with less vision improvement and an increased risk of vision-impairing central-involved DME developing. When managing PDR with ranibizumab, eyes gained vision, on average, with no baseline characteristics identified as associated with visual acuity or central-involved DME outcomes.

Factors Associated with Worsening Proliferative Diabetic Retinopathy in Eyes Treated with Panretinal Photocoagulation or Ranibizumab.

PURPOSE: To compare rates and identify predictive factors for events that represent worsening of proliferative diabetic retinopathy (PDR) in eyes treated with panretinal photocoagulation (PRP) or ranibizumab. DESIGN: Randomized clinical trial (55 United States sites). PARTICIPANTS: Three hundred ninety-four study eyes from 305 adults with PDR, visual acuity (VA) 20/320 or better, and no history of PRP. INTERVENTION: Panretinal photocoagulation or intravitreous ranibizumab injections (0.5 mg/0.05 ml). MAIN OUTCOME MEASURES: Time from randomization to a composite PDR-worsening outcome defined as the first occurrence of vitreous hemorrhage, retinal detachment, anterior segment neovascularization, or neovascular glaucoma. RESULTS: Through 2 years, the cumulative probability of worsening PDR was 42% (PRP) versus 34% (ranibizumab; hazard ratio [HR], 1.33; 99% confidence interval [CI], 0.90 to 1.98; P = 0.063). Worse baseline levels of diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study scale) were associated with increased risk of worsening PDR, regardless of treatment group (64% [high-risk PDR or worse] vs. 23% [moderate PDR or better]; HR, 3.97; 99% CI, 2.48 to 6.36; P < 0.001). In the PRP group, eyes receiving pattern scan versus conventional single-spot PRP also were at higher risk for worsening PDR (60% vs. 39%; HR, 2.04; 99% CI, 1.02 to 4.08; P = 0.008), regardless of the number of spots placed or the number of sittings to complete the initial PRP. Eyes in both groups with vision-impairing (VA 20/32 or worse) center-involved diabetic macular edema (DME) at baseline were required to receive ranibizumab for center-involved DME. Therefore the composite outcome was compared by treatment in the subgroup of eyes that did not have vision-impairing center-involved DME at baseline. For these eyes, the rate of PDR-worsening was greater with PRP than ranibizumab (45% vs. 31%; HR, 1.62; 99% CI, 1.01 to 2.60; P = 0.008). CONCLUSIONS: In eyes with PDR, ranibizumab resulted in less PDR worsening compared with PRP, especially in eyes not required to receive ranibizumab for center-involved DME. Although anti-vascular endothelial growth factor therapy requires a more frequent visit schedule than PRP, these findings provide additional evidence supporting the use of ranibizumab as an alternative therapy to PRP for PDR, at least through 2 years.

Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Patient-Centered Outcomes From a Randomized Clinical Trial.

PURPOSE: To compare patient-centered outcomes in patients with proliferative diabetic retinopathy (PDR) treated with ranibizumab vs panretinal photocoagulation (PRP). DESIGN: Randomized clinical trial. METHODS: Setting: Multicenter (55 U.S. sites). PATIENT POPULATION: Total of 216 adults with 1 study eye out of 305 adults (excluding participants with 2 study eyes, because each eye received a different treatment) with PDR, visual acuity 20/320 or better, no history of PRP. INTERVENTION: Ranibizumab (0.5 mg/0.05 mL) vs PRP. MAIN OUTCOME MEASURES: Change from baseline to 2 years in composite and prespecified subscale scores from the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), University of Alabama Low Luminance Questionnaire (UAB-LLQ), and Work Productivity and Activity Impairment Questionnaire (WPAIQ). RESULTS: For the NEI VFQ-25 and UAB-LLQ composite scores, ranibizumab-PRP treatment group differences (95% CI) were +4.0 (-0.2, +8.3, P = .06) and +1.8 (-3.5, +7.1, P = 0.51) at 1 year, and +2.9 (-1.5, +7.2, P = .20) and +2.3 (-2.9, +7.5, P = .37) at 2 years, respectively. Work productivity loss measured with the WPAIQ was 15.6% less with ranibizumab (-26.3%, -4.8%, P = .005) at 1 year and 2.9% (-12.2%, +6.4%, P = .54) at 2 years. Eighty-three ranibizumab participants (97%) were 20/40 or better in at least 1 eye (visual acuity requirement to qualify for an unrestricted driver's license in many states) at 2 years compared with 82 PRP participants (87%, adjusted risk ratio = 1.1, 95% CI: 1.0, 1.2, P = .005). CONCLUSIONS: Though differences in some work productivity and driving-related outcomes favored ranibizumab over PRP, no differences between treatment regimens for PDR were identified for most of the other patient-centered outcomes considered.

Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.

IMPORTANCE: Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE: To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS: Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES: The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS: Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE: Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01489189.

Clinical Course of Vitreomacular Traction Managed Initially by Observation.

BACKGROUND AND OBJECTIVE: To investigate the clinical course and outcomes of patients with vitreomacular traction (VMT) managed initially by observation. PATIENTS AND METHODS: This noncomparative case series included patients with a diagnosis of VMT based on clinical symptoms and findings on spectral-domain optical coherence tomography (SD-OCT) between 2005 and 2014. VMT was documented using a standardized grading system based on the degree of distortion of the foveal contour. Data were collected at five retina clinics using standardized collection forms. Visual acuity, changes in SD-OCT findings, and timing of the release of VMT as seen on SD-OCT were recorded. RESULTS: The study included 230 eyes of 185 patients. Mean age was 72.5 years, and mean follow-up was 32 months. At baseline, VMT grading was grade 1 in 92 eyes (40%), grade 2 in 118 eyes (51.3%), and grade 3 in 20 eyes (8.7%). By last follow-up, spontaneous release of VMT occurred in 73 eyes (31.7%). Spontaneous release of VMT occurred at a mean of 18 months (median: 10.9 months) after initial visit. Mean logMAR best corrected visual acuity (BCVA) was 0.28 (20/55) (range: 20/20 to 20/400) at baseline and 0.25 (20/51) (range: 20/20 to 20/400) at last follow-up. Pars plana vitrectomy was performed in 10 eyes (4.1%) for macular hole (six eyes) and increased VMT (four eyes); BCVA was at least 20/40 in eight of the 10 eyes at last follow-up. CONCLUSION: Patients with VMT generally had a favorable clinical course when managed initially by observation. Spontaneous release of VMT occurred in approximately one-third of patients. At last follow-up, pars plana vitrectomy was performed in fewer than 5% of patients.

Optical coherence tomography-measured pigment epithelial detachment height as a predictor for retinal pigment epithelial tears associated with intravitreal bevacizumab injections.

PURPOSE: The purpose was to study preinjection optical coherence tomography-related factors in age-related macular degeneration eyes with retinal pigment epithelial detachment (PED) that may predispose retinal pigment epithelial (RPE) tears associated with intravitreal bevacizumab injections. METHODS: This multicenter retrospective case series involving 9 retina specialists and 7 centers investigated Stratus optical coherence tomography (Carl Zeiss Meditec, Dublin, CA) parameters in eyes with vascularized PED (vPED) from February 2006 to February 2007. Of the 1,280 eyes in 1,255 patients receiving 2,890 intravitreal injections, there were 125 eyes with vPED. For every vPED eye that developed an RPE tear (Group 1), 3 or more vPED eyes without RPE tears (Group 2) were randomly selected in each study center during the same time period for comparison. The primary outcome measure was PED height (microm), and the secondary measures included volume index (vPED height x surface area), total macular volume, subretinal fluid, cystoid macular edema, center-point thickness, central 1 mm, and pre- and postinjection best-corrected Snellen visual acuities. RESULTS: Twenty-one vPED eyes in 21 patients among 125 vPED eyes (16.8% of all vPED eyes) developed RPE tears. The 21 Group 1 eyes were compared with the 78 randomly selected Group 2 eyes. The vPED height was significantly higher for Group 1 eyes in comparison to Group 2 eyes (mean: 648.9 +/- 245.0 vs. 338.1 +/- 201.6 microm, P < 0.001). The same was true for the following: volume index (P = 0.001), subretinal fluid (P = 0.002), and total macular volume (P = 0.04). The mean preinjection and post-RPE tear best-corrected visual acuity were 0.92 logMAR (20/166) and 0.84 logMAR (20/137), respectively (P = 0.25). Multivariate analysis showed PED height to be the only significant risk factor associated with RPE tears in Group 1 eyes [odds ratio = 0.995 (95% confidence interval: 0.992-0.997), P < 0.001]. CONCLUSION: Elevated preinjection vPED height is the single most significant predictor for RPE tears after bevacizumab injections for vPED eyes. A vPED height >400 microm is associated with a significant risk for such a complication.

Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings.

OBJECTIVE: To compare the effects of single-sitting vs 4-sitting panretinal photocoagulation (PRP) on macular edema in subjects with severe nonproliferative or early proliferative diabetic retinopathy with relatively good visual acuity and no or mild center-involved macular edema. METHODS: Subjects were treated with 1 sitting or 4 sittings of PRP in a nonrandomized, prospective, multicentered clinical trial. Main Outcome Measure Central subfield thickness on optical coherence tomography (OCT). RESULTS: Central subfield thickness was slightly greater in the 1-sitting group (n = 84) than in the 4-sitting group (n = 71) at the 3-day (P = .01) and 4-week visits (P = .003). At the 34-week primary outcome visit, the slight differences had reversed, with the thickness being slightly greater in the 4-sitting group than in the 1-sitting group (P = .06). Visual acuity differences paralleled OCT differences. CONCLUSIONS: Our results suggest that clinically meaningful differences are unlikely in OCT thickness or visual acuity following application of PRP in 1 sitting compared with 4 sittings in subjects in this cohort. More definitive results would require a large randomized trial. Application to Clinical Practice These results suggest PRP costs to some patients in terms of travel and lost productivity as well as to eye care providers could be reduced. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00687154.

Retinal thickness on Stratus optical coherence tomography in people with diabetes and minimal or no diabetic retinopathy.

PURPOSE: To evaluate optical coherence tomography (OCT) thickness of the macula in people with diabetes but minimal or no retinopathy and to compare these findings with published normative data in the literature from subjects reported to have no retinal disease. DESIGN: Cross-sectional study. METHODS: In a multicenter community- and university-based practices setting, 97 subjects with diabetes with no or minimal diabetic retinopathy and no central retinal thickening on clinical examination and a center point thickness of 225 microm or less on OCT (Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA) were recruited. Electronic Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, seven-field stereoscopic color fundus photographs, and Stratus OCT fast macular scan were noted. Main outcome measures were central subfield (CSF) thickness measured on Stratus OCT. RESULTS: On average, CSF thickness was 201 +/- 22 microm. CSF thickness was significantly greater in retinas from men than retinas from women (mean +/- standard deviation, 209 +/- 18 microm vs 194 +/- 23 microm; P < .001). After adjusting for gender, no additional factors were found to be associated significantly with CSF thickness (P > .10). CONCLUSIONS: CSF thicknesses on Stratus OCT in people with diabetes and minimal or no retinopathy are similar to thicknesses reported from a normative database of people without diabetes. CSF thickness is greater in men than in women, consistent with many, but not all, previous reports. Studies involving comparisons of retinal thickness with expected norms should consider different mean values for women and men.

Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration.

PURPOSE: To study retinal pigment epithelium (RPE) tears after off-label intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) injection for neovascular age-related macular degeneration. Eyes with a vascularized pigment epithelial detachment (PED) that developed an RPE tear were compared with eyes with a vascularized PED but without an RPE tear. METHODS: Nine retina specialists across the United States and in Europe participated in this retrospective case series. All eyes that received intravitreal bevacizumab injection for choroidal neovascularization (CNV) over 12 months (October 2005 to September 2006) were included. Eyes without all three confirmed tests (fluorescein angiography, fundus photography, and optical coherence tomography) were excluded from analysis. Statistical analyses were performed on multiple characteristics of eyes with a vascularized PED that did and did not develop an RPE tear. RESULTS: Among 2,785 intravitreal bevacizumab injections for 1,064 eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15, 100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean subfoveal PED size was larger for eyes with tears than for those without tears (13.97 mm vs 9.9 mm, respectively; P = 0.01; odds ratio, 1.09). There was substantially smaller mean ratio of CNV size to PED size for eyes with tears than for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre-bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean post-RPE tear best-corrected visual acuity was 20/160 (P = 0.48). CONCLUSION: Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.

Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema.

PURPOSE: To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME). DESIGN: Prospective 1-day observational study. PARTICIPANTS: Two hundred twelve eyes of 107 patients with DME involving the macular center by clinical examination and OCT central subfield thickness of > or =225 microm. METHODS: Retinal thickness was measured with the OCT3 system, and scans were evaluated by a reading center. Reproducibility of retinal thickness measurements was assessed, and 95% confidence intervals (CIs) for a change in thickness were estimated. MAIN OUTCOME MEASURES: Reproducibility of OCT-measured central subfield thickness. RESULTS: Reproducibility was better for central subfield thickness than for center point thickness (half-width of the 95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11% vs. 17%, respectively; P<0.001). The median absolute difference between replicate measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI for a change in central subfield thickness were 22, 23, 33, and 56 microm for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. When expressed as percentage differences between 2 measurements, half-widths of the 95% CI for a change in central subfield thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were unable to identify an effect on reproducibility of central subfield measurements with respect to the presence of cystoid abnormalities, subretinal fluid, vitreomacular traction, or reduced visual acuity. Reproducibility was better when both scans had a standard deviation (SD) of the center point of <10.0% (half-width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001). CONCLUSIONS: Reproducibility is better for central subfield thickness measurements than for center point measurements, and variability is less with retinal thickness when expressed as a percent change than when expressed as an absolute change. A change in central subfield thickness exceeding 11% is likely to be real. Scans with an SD of the center point of > or =10.0% are less reproducible and should be viewed with caution when assessing the validity of an observed change in retinal thickness in patients with DME.