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Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy.

IMPORTANCE: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices. OBJECTIVE: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020. INTERVENTIONS: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria. MAIN OUTCOMES AND MEASURES: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage. RESULTS: A total of 205 eyes were included in the analysis (115 male [56%] and 90 [44%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was −4.3 (95% CI, −10.6 to 1.9) compared with −16.7 (95% CI, −24.4 to −9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95% CI, 20-32] weeks; P < .001). CONCLUSIONS AND RELEVANCE: Both initial aflibercept and vitrectomy with PRP are viable treatment approaches for PDR-related vitreous hemorrhage. Although this study did not find a significant difference between groups in the primary outcome of mean VA over 24 weeks of follow-up, eyes receiving initial vitrectomy with PRP had faster recovery of vision over 24 weeks when baseline VA was worse than 20/800 and faster vitreous hemorrhage clearance. Approximately one-third of the eyes in each group received the alternative treatment (aflibercept or vitrectomy with PRP). These factors may influence treatment decisions for patients initiating therapy for PDR-related vitreous hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02858076

IMPORTANCE: The role of anti–vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. OBJECTIVE: To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. DESIGN, SETTING, AND PARTICIPANTS: Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. INTERVENTIONS: Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. MAIN OUTCOMES AND MEASURES: Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. RESULTS: Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50; P < .001), favoring aflibercept. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs 33.2% in the sham group, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs 14.8% in the sham group. The mean (SD) change in visual acuity from baseline to 2 years was −0.9 (5.8) letters with aflibercept and −2.0 (6.1) letters with sham (adjusted mean difference, 0.5 letters [97.5% CI, −1.0 to 1.9 letters]; P = .47). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02634333

OPT-302 is a novel inhibitor of vascular endothelial growth factor (VEGF)-C and VEGF-D. A phase 1 trial assessed the safety of intravitreal OPT-302 as monotherapy or combined with ranibizumab (Lucentis; Genentech, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD).

To assess the feasibility of daily Home OCT imaging among patients with neovascular age-related macular degeneration (nAMD).

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

IMPORTANCE: Macular edema (ME) is the leading cause of decreased visual acuity (VA) associated with retinal vein occlusion (RVO). Identifying factors associated with better outcomes in RVO eyes treated with anti–vascular endothelial growth factor (VEGF) therapy may provide information useful in counseling patients. OBJECTIVE: To investigate baseline characteristics associated with 6-month VA and central subfield thickness (CST) outcomes in participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). DESIGN, SETTING, AND PARTICIPANTS: A total of 362 patients with central RVO or hemi-RVO were enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in a masked fashion to receive bevacizumab or aflibercept. At month 6, 348 participants (96%) had VA outcomes measured and 335 participants (93%) had spectral domain optical coherence tomography outcomes measured. The current data analysis was conducted from February 27, 2017, to April 7, 2017. INTERVENTIONS: Eyes were randomly assigned to receive an intravitreal injection of bevacizumab, 1.25 mg, or aflibercept, 2.0 mg, at baseline and every 4 weeks, with the primary outcome measured at 6 months. MAIN OUTCOMES AND MEASURES: Change from baseline in VA letter score (VALS), VALS gain of 15 or more, change from baseline in CST, CST less than 300 µm, and resolution of ME. Baseline factors associated with 6-month outcome at the 0.05 level in univariate regressions were included in multivariate regressions, with those significant after multiplicity control by the Hochberg method reported. RESULTS: The mean (SD) age of patients was 69 (12) years, and 43% were women. Younger patient age (odds ratio [OR], 0.95 per year of age; 95% CI, 0.93-0.98; P = .007) and lower baseline VALS (OR, 0.96 per letter; 95% CI, 0.94-0.98; P < .001) were associated with a 6-month VALS gain of 15 or greater. Compared with bevacizumab, aflibercept treatment was associated with a higher odds of ME resolution (OR, 3.59; 95% CI, 2.22-5.80; P < .001) and CST less than 300 µm (OR,  5.30; 95% CI, 2.40-11.67; P = .001), but not with a better VA outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF treatment prior to study participation (OR, 0.33; 95% CI, 0.17-0.64; P = .03). CONCLUSIONS AND RELEVANCE: In eyes treated with bevacizumab or aflibercept, younger age and worse baseline VALS were associated with better 6-month VA outcomes. Aflibercept treatment was associated with more favorable spectral domain optical coherence tomography outcomes but not VA outcomes. These findings may be useful in assessing expected response at month 6 after monthly injection of anti-VEGF agents for treating ME due to CRVO and HRVO. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01969708

IMPORTANCE: Comparisons of the relative effect of 3 anti–vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment. OBJECTIVE: To provide additional outcomes from a randomized trial evaluating 3 anti–vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography. DESIGN, SETTING, AND PARTICIPANTS: Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015. INTERVENTIONS: Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. MAIN OUTCOMES AND MEASURES: One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 µm) or thinner (250 to 399 µm) CST. RESULTS: In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17% to 60%) for aflibercept vs bevacizumab, 25% (5% to 46%) for ranibizumab vs bevacizumab, and 13% (–8% to 35%) for aflibercept vs ranibizumab. CONCLUSIONS AND RELEVANCE: These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627249.

IMPORTANCE: Optimization of glycemic control is critical to reduce the number of diabetes mellitus–related complications, but long-term success is challenging. Although vision loss is among the greatest fears of individuals with diabetes, comprehensive personalized diabetes education and risk assessments are not consistently used in ophthalmologic settings. OBJECTIVE: To determine whether the point-of-care measurement of hemoglobin A1c (HbA1c) and personalized diabetes risk assessments performed during retinal ophthalmologic visits improve glycemic control as assessed by HbA1c level. DESIGN, SETTING, AND PARTICIPANTS: Ophthalmologist office–based randomized, multicenter clinical trial in which investigators from 42 sites were randomly assigned to provide either a study-prescribed augmented diabetes assessment and education or the usual care. Adults with type 1 or 2 diabetes enrolled into 2 cohorts: those with a more-frequent-than-annual follow-up (502 control participants and 488 intervention participants) and those with an annual follow-up (368 control participants and 388 intervention participants). Enrollment was from April 2011 through January 2013. INTERVENTIONS: Point-of-care measurements of HbA1c, blood pressure, and retinopathy severity; an individualized estimate of the risk of retinopathy progression derived from the findings from ophthalmologic visits; structured comparison and review of past and current clinical findings; and structured education with immediate assessment and feedback regarding participant’s understanding. These interventions were performed at enrollment and at routine ophthalmic follow-up visits scheduled at least 12 weeks apart. MAIN OUTCOMES AND MEASURES: Mean change in HbA1c level from baseline to 1-year follow-up. Secondary outcomes included body mass index, blood pressure, and responses to diabetes self-management practices and attitudes surveys. RESULTS: In the cohort with more-frequent-than-annual follow-ups, the mean (SD) change in HbA1c level at 1 year was −0.1% (1.5%) in the control group and −0.3% (1.4%) in the intervention group (adjusted mean difference, −0.09% [95% CI, −0.29% to 0.12%]; P = .35). In the cohort with annual follow-ups, the mean (SD) change in HbA1c level was 0.0% (1.1%) in the control group and −0.1% (1.6%) in the intervention group (mean difference, −0.05% [95% CI, −0.27% to 0.18%]; P = .63). Results were similar for all secondary outcomes. CONCLUSIONS AND RELEVANCE: Long-term optimization of glycemic control is not achieved by a majority of individuals with diabetes. The addition of personalized education and risk assessment during retinal ophthalmologic visits did not result in a reduction in HbA1c level compared with usual care over 1 year. These data suggest that optimizing glycemic control remains a substantive challenge requiring interventional paradigms other than those examined in our study. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01323348

IMPORTANCE The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina. OBJECTIVE To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING, PARTICIPANTS The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye. INTERVENTIONS In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. MAIN OUTCOMES AND MEASURES Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy. CONCLUSION AND RELEVANCE The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00345176

IMPORTANCE Age-related cataract is a leading cause of visual impairment in the United States. The prevalence of age-related cataract is increasing, with an estimated 30.1 million Americans likely to be affected by 2020. OBJECTIVE To determine whether daily oral supplementation with lutein/zeaxanthin affects the risk for cataract surgery. DESIGN, SETTING, AND PATIENTS The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, double-masked clinical trial, enrolled 4203 participants, aged 50 to 85 years, at risk for progression to advanced age-related macular degeneration. INTERVENTIONS Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10mg/2mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination to evaluate the effects on the primary outcome of progression to advanced age-related macular degeneration. MAIN OUTCOMES AND MEASURES Cataract surgery was documented at annual study examination with the presence of pseudophakia or aphakia, or reported during telephone calls at 6-month intervals between study visits. Annual best-corrected visual acuity testing was performed. A secondary outcome of AREDS2 was to evaluate the effects of lutein/zeaxanthin on the subsequent need for cataract surgery. RESULTS A total of 3159 AREDS2 participants were phakic in at least 1 eye and 1389 of 6027 study eyes underwent cataract surgery during the study, with median follow-up of 4.7 years. The 5-year probability of progression to cataract surgery in the no lutein/zeaxanthin group was 24%. For lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratios for progression to cataract surgery was 0.96 (95% CI, 0.84-1.10; P = .54). For participants in the lowest quintile of dietary intake of lutein/zeaxanthin, the hazard ratio comparing lutein/zeaxanthin vs no lutein/zeaxanthin for progression to cataract surgery was 0.68 (95% CI, 0.48-0.96; P = .03). The hazard ratio for 3 or more lines of vision loss was 1.03 (95% CI, 0.93-1.13; P = .61 for lutein/zeaxanthin vs no lutein/zeaxanthin). CONCLUSIONS AND RELEVANCE Daily supplementation with lutein/zeaxanthin had no statistically significant overall effect on rates of cataract surgery or vision loss. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00345176.

The effects of periodical focusing of light were studied in chains of sapphire microspheres with 300 m diameters assembled either on a substrate or inside capillary tubing. Dye-doped fluorescent microspheres were used as multimodal sources of light in experimental studies. Significant reduction of the focused spot sizes was observed for chains of spheres compared to a single sphere case. Numerical ray tracing simulations were performed for similar chains assembled inside hollow waveguides to be used as an optical delivery system with mid-infrared lasers for ultra-precise surgery. The device designs were optimized for contact conditions during laser surgery involving short optical penetration depths of light in tissue. It is shown that chains of spheres with n around 1.65-1.75 provide a two-fold improvement of the spatial resolution over single spheres. Potential applications of these microprobes include ultraprecise laser procedures in the eye and brain or piercing a cell, and coupling of multimodal beams into photonic microstructures.

OBJECTIVE To describe characteristics of the Age-Related Eye Disease Study (AREDS) 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). METHODS Eligibility criteria for CAPT required 10 or more large (≥125 μm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs. RESULTS Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline. CONCLUSIONS The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.Arch Ophthalmol. 2009;127(9):1147-1151--

OBJECTIVE To assess changes in electroretinography (ERG) and other retinal function parameters during 6 months of daily use of tadalafil, sildenafil citrate, or placebo. METHODS Subjects were randomized to use of a placebo (n = 82), 5 mg of tadalafil (n = 85), or 50 mg of sildenafil (n = 77) daily for 6 months. Electroretinographs were recorded using the International Society for Clinical Electrophysiology of Vision (ISCEV) protocol and standardized ERG equipment at all 15 study sites. Other tests of ocular anatomy and visual function were performed at each assessment. MAIN OUTCOME MEASURES The primary outcome was the average mean change for both eyes from baseline to endpoint in ERG b-wave amplitude using dark-adapted combined standard response to a bright ISCEV standard flash. Secondary endpoints were other ERG parameter changes, visual acuity, number of errors in color discrimination testing, mean deviation in automated visual field testing, and intraocular pressure (IOP). RESULTS No significant differences were found between treatment/placebo groups for the primary outcome, most other ERG variables, visual function, IOP, or anatomic assessments. The medications were well tolerated. CONCLUSIONS No abnormalities in ERG or visual function and no treatment-related findings suggestive of drug toxicity are associated with daily administration of tadalafil or sildenafil for 6 months. APPLICATION TO CLINICAL PRACTICE Assessed visual safety of tadalafil/sildenafil administered daily over a prolonged period. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00333281Arch Ophthalmol. 2009;127(4):367-373--

To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration.

Corticosteroids, alone or in combination with other drugs, have been shown to inhibit angiogenesis. The purpose of this study was to evaluate the efficacy of triamcinolone acetonide in a new model of preretinal neovascularization. Rabbit eyes were treated with intravitreal triamcinolone acetonide 24 h before partial liquefaction of the posterior vitreous with hyaluronidase and injection of 250000 homologous tissue-cultured dermal fibroblasts. Triamcinolone acetonide effectively inhibited new vessel growth in treated eyes. Only 14% of the treated eyes developed new blood vessels compared to 100% of sham-injected control eyes (P<0.001). These results suggest that intravitreal triamcinolone acetonide might be effective in inhibiting new vessel growth in patients with inflammatory retinal neovascularization, such as that associated with sarcoidosis or other uveitic syndromes.

Ophthalmic surgery may benefit from the use of more precise fiber delivery systems for laser surgery. In this study, chains of sapphire microspheres integrated into the distal tip of a hollow waveguide are used for preliminary mid-infrared, Erbium:YAG laser ablation studies in contact mode with ophthalmic tissues, ex vivo. The combination of the Er:YAG laser's short optical penetration depth and small spot diameters achieved with this novel fiber probe may provide more precise tissue removal. One, three, and five microsphere chain structures were assembled and compared, resulting in spot diameters of 67, 32, and 30 m, respectively. Single laser pulses of 0.1 mJ energy and 75 s duration produced craters with average widths of 44, 30, and 17 m and depths of 26, 10, and 8 m, for one, three, and five sphere structures, respectively. Chains of microspheres produced spatial filtering of the multimode Er:YAG laser beam and fiber, thus providing spot diameters not otherwise available for precise tissue ablation using conventional fiber delivery systems. With further probe development, this novel approach to mid-IR laser ablation may provide an alternative to mechanical tools for ultra-precise surgical dissection and removal of ophthalmic tissues.