Objective To report 5-year results from a previously reported trial evaluating intravitreal 0.5-mg ranibizumab with prompt versus deferred (for ≥24 weeks) focal/grid laser treatment for diabetic macular edema (DME). Design Multicenter randomized clinical trial. Participants Among participants from the trial with 3 years of follow-up who subsequently consented to a 2-year extension and survived through 5 years, 124 (97%) and 111 (92%) completed the 5-year visit, in the prompt and deferred groups, respectively. Methods Random assignment to ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and either prompt or deferred (>= 24 weeks) focal/grid laser treatment. Main Outcome Measures Best-corrected visual acuity at the 5-year visit. Results The mean change in visual acuity letter score from baseline through the 5-year visit was +7.2 letters in the prompt laser group compared with +9.8 letters in the deferred laser group (mean difference -2.6 letters, 95% confidence interval -5.5 to +0.4 letters, P = 0.09). At the 5-year visit in the prompt vs. deferred laser groups respectively, there was vision loss of ≥10 letters in 9% vs. 8%, an improvement of ≥10 letters in 46% vs. 58%, and an improvement of >15 letters in 27% vs. 38% of participants. From baseline through 5 years, 56% of participants in the deferred group did not receive laser. The median number of injections was 13 vs. 17 in the prompt and deferral groups, including 54% and 45% receiving no injections during year 4 and 62% and 52% receiving no injections during year 5, respectively. Conclusions Five-year results suggest focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better than deferring laser treatment for ≥24 weeks in eyes with DME involving the central macula with vision impairment. While over half of eyes where laser treatment is deferred may avoid laser for at least 5 years, such eyes may require more injections to achieve these results when following this protocol. Most eyes treated with ranibizumab and either prompt or deferred laser maintain vision gains obtained by the first year through 5 years with little additional treatment after 3 years.

Objective To evaluate the association of subretinal hyper-reflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar in the Comparison of Age related Macular Degeneration Treatments Trials (CATT) Design Prospective cohort study within a randomized clinical trial. Participants The 1185 participants in CATT. Methods Participants were randomly assigned to ranibizumab or bevacizumab treatment monthly or as-needed. Masked readers graded scar and GA on fundus photography and fluorescein angiography images, SHRM on time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1mm2, or outside the center 1mm2 were obtained on SD-OCT images at 56 (n=76) and 104 (n=66) weeks. VA was measured by certified examiners. Main Outcome Measures SHRM presence, location and size, and associations with VA, scar, and GA. Results Among all CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than eyes with SHRM that resolved (64% vs. 31%; p<0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n=76) and 104 (n=66), mean [SE] VA letter score was 73.5 [2.8], 73.1 [3.4], 65.3 [3.5], and 63.9 [3.7] when SHRM was absent, present outside the central 1mm2, present within the central 1mm2 but not the foveal center, or present at the foveal center (p=0.02). SHRM was present at the foveal center in 43 (30%), within the central 1mm2 in 21 (15%) and outside the central 1mm2 in 19 (13%). When SHRM was present, the median maximum height in microns under the fovea, within the central 1 mm2 including the fovea and anywhere within the scan was 86; 120; and 122, respectively. VA was decreased with greater SHRM height and width (p<0.05). Conclusions SHRM is common in eyes with NVAMD and often persists after anti-VEGF treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM height and width were associated with worse VA. SHRM is an important morphological biomarker in eyes with NVAMD.

Hybrid elements containing optical power with both diffractive (holographic) and refractive components are shown to be useful for obtaining arbitrary or, in special cases, achromatic dispersive characteristics. In one configuration a volume holographic element is coated on the surface of a crown glass lens, and by varying the power distributions among the refractive and holographic components while maintaining constant overall optical power the effective Abbe V numbers of the resultant hybrid element are shown to span all real numbers excepting a narrow interval around zero. In the achromat case (V number = infinity), both refractive and diffractive components are of the same sign resulting in much smaller glass curvatures than in all-refractive achromat doublets or apochromat triplets. The large separation between holographic partial dispersions and available glass partial dispersions is shown to lead to hybrid three-color achromats with greatly reduced glass curvatures. Applications are expected to include broadband achromatic objectives and chromatic aberration corrector plates in high performance optical systems. Such corrector plates may have any net power (including zero) while exhibiting effective V numbers that are positive or negative and that span a wide range, e.g., +/-1 or +/-1000. Further advantages include reducing the need for choosing high dispersion glasses, which may be costly and difficult to grind or polish. High diffraction efficiency and broad spectral bandwidths (in excess of 3000 A) are obtained in the holographic optical elements using single-element central-stop and cascaded element designs.

Purpose-To evaluate optical coherence tomography thickness of the macula in people with diabetes but minimal or no retinopathy and compare these findings with published normative data in the literature from subjects reported to have no retinal disease.Design-Cross-sectional study.• Setting: Multicenter, community-and university-based practices.• Study Population: 97 subjects with diabetes with no or minimal diabetic retinopathy and no central retinal thickening on clinical examination and a center point thickness ≤225 microns on a Stratus™ (Carl Zeiss Meditec, Dublin, CA) optical coherence tomography (Stratus OCT™).• Observation Procedures: Electronic-ETDRS best-corrected visual acuity, 7-field stereoscopic color fundus photographs, Stratus OCT™ fast macular scan.• Main Outcome Measures: Central subfield thickness measured on Stratus OCT™.Results-On average, central subfield thickness was 201 ± 22 microns. Central subfield thickness was significantly greater in retinas from men than retinas from women subjects (mean 209 ± 18 microns versus 194 ± 23 microns, P<0.001). After adjusting for gender, no additional factors were found to be significantly associated with central subfield thickness (P>0.10).Conclusions-Central subfield 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. Central subfield thickness is greater in men than in women, consistent with many, but not all, previous reports. Studies involving comparisons of retinal thickness to expected norms should consider different mean values for women and men.

Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

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Purpose To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period. Methods In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 lm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 lm from baseline and a CPT of at least 300 lm, or treatment for DME (performed at the discretion of the investigator). Results The cumulative probability of meeting an increase in OCT CPT of at least 50 lm from baseline and a CPT of at least 300 lm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years. Conclusions Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification.

This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.