Visual Acuity Letter Score Research Articles

RANIBIZUMAB FOR MACULAR TELANGIECTASIA TYPE 2 IN THE ABSENCE OF SUBRETINAL NEOVASCULARIZATION

To evaluate the effects of 0.3 mg or 0.5 mg of ranibizumab in eyes with macular telangiectasia type 2 without subretinal neovascularization. Ten eyes were randomized to either 0.3 mg or 0.5 mg ranibizumab group in 1 eye only. Study eye received ranibizumab at baseline and at Months 1 and 2. Injections at Months 3, 4, and 5 were at investigator's discretion. Participants were followed monthly through 6 months with best-corrected visual acuity, fluorescein angiography, and optical coherence tomography. For study eyes at baseline, median best-corrected visual acuity letter score was 60 (20/64 Snellen equivalent) and central subfield retinal thickness was 181.5 μm. Median number of injections was six. Median change in best-corrected visual acuity at Month 3 was 4 letters (range: -5 to 9 letters) at both doses in the study eye and 3 letters (range: -10 to 5 letters) in the untreated fellow eye. At Month 3, retinal leakage decreased 0.87 disk area and 0.76 disk area for 0.3 mg and 0.5 mg ranibizumab, respectively. Median change in central subfield retinal thickness was 1 μm and -11 µm for 0.3 mg and 0.5 mg ranibizumab, respectively. Ranibizumab (0.3 mg or 0.5 mg) decreases leakage secondary to macular telangiectasia type 2, but accompanying improvements in best-corrected visual acuity appear similar to improvements in the untreated fellow eye where retinal thickness is relatively unchanged.

Safety and Efficacy of Conbercept in Neovascular Age-Related Macular Degeneration: Results from a 12-Month Randomized Phase 2 Study: AURORA Study

To assess the safety and efficacy of multiple injections of 0.5 and 2.0 mg conbercept using variable dosing regimens in patients with neovascular age-related macular degeneration (AMD). Randomized, double-masked, multicenter, controlled-dose, and interval-ranging phase 2 clinical trial divided into a 3-month loading phase followed by a maintenance phase. Patients with choroidal neovascularization secondary to AMD with lesion sizes of 12 disc areas or less and a best-corrected visual acuity (BCVA) letter score of between 73 and 24 were enrolled. Patients were randomized 1:1 to receive either 0.5 or 2.0 mg intravitreal conbercept for 3 consecutive monthly does. After the third dose, each group was reassigned randomly again to monthly (Q1M group) or as-needed (pro re nata [PRN] group) treatment without changing the drug assignment. The primary end point was the mean change in BCVA from baseline to month 3, with secondary end points being the mean change in BCVA, mean change in central retinal thickness (CRT), and safety at month 12. We enrolled 122 patients. At the primary end point at month 3, mean improvements in BCVA from baseline in the 0.5- and 2.0-mg groups were 8.97 and 10.43 letters, respectively. At month 12, mean improvements in BCVA from baseline were 14.31, 9.31, 12.42, and 15.43 letters for the 0.5-mg PRN, 0.5-mg Q1M, 2.0-mg PRN, and 2.0-mg Q1M regimens, respectively. At month 12, mean reductions in CRT in the 4 regimens were 119.8, 129.7, 152.1, and 170.8 μm, respectively. There were no significant differences for the pairwise comparisons between all study groups. The difference in the number of injections between the 2 PRN groups was not statistically significant. Treatment with conbercept generally was safe and well tolerated. The significant gains in BCVA at 3 months were the same or better at 12 months in all conbercept dosing groups of neovascular AMD patients. During the 12 months, repeated intravitreal injections of conbercept were well tolerated in these patients. Future clinical trials are required to confirm its long-term efficacy and safety.

GREEN OR YELLOW LASER TREATMENT FOR DIABETIC MACULAR EDEMA

Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 ± 14 and +5.1 ± 13 at the 52-week visit (P = 0.06) and +2.4 ± 15 and +6.0 ± 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.

Macular Edema After Cataract Surgery in Eyes Without Preoperative Central-Involved Diabetic Macular Edema

The incidence of development or worsening of macular edema (ME) is variable in eyes without diabetic ME (DME) undergoing cataract surgery. To estimate the incidence of central-involved ME 16 weeks following cataract surgery in eyes with diabetic retinopathy without definite central-involved DME preoperatively. In a multicenter, prospective, observational study, 293 participants with diabetic retinopathy without definite central subfield thickening on optical coherence tomography (OCT) underwent cataract surgery. Cataract extraction surgery performed within 28 days of enrollment of eyes without DME in individuals with diabetes mellitus. Development of central-involved ME defined as the following: (1) OCT central subfield thickness of 250 μm or greater (time-domain OCT) or 310 μm or greater (spectral-domain OCT) with at least a 1-step increase in logOCT central subfield thickness preoperatively to the 16-week visit; (2) at least a 2-step increase in logOCT central subfield thickness preoperatively to the 16-week visit; or (3) nontopical treatment for ME received before the 16-week visit with either of the OCT criteria met at the time of treatment. The median participant age was 65 years. The median visual acuity letter score was 69 letters (Snellen equivalent 20/40). Forty-four percent of eyes had a history of treatment for DME. Sixteen weeks postoperatively, central-involved ME was noted in 0% (95% CI, 0%-20%) of 17 eyes with no preoperative DME. Of eyes with non-central-involved DME, 10% (95% CI, 5%-18%) of 97 eyes without central-involved DME and 12% (95% CI, 7%-19%) of 147 eyes with possible central-involved DME at baseline progressed to central-involved ME. History of DME treatment was significantly associated with central-involved ME development (P < .001). In eyes with diabetic retinopathy without concurrent central-involved DME, presence of non-central-involved DME immediately prior to cataract surgery or history of DME treatment may increase the risk of developing central-involved ME 16 weeks after cataract extraction.

Reading Speed Improvements in Retinal Vein Occlusion After Ranibizumab Treatment

Treatment of macular edema secondary to retinal vein occlusion with ranibizumab has been shown to improve visual acuity compared with macular laser or observation. It is important to determine whether these visual acuity improvements translate into measurable improvements in visual function. To examine the benefit of ranibizumab (Lucentis) on measured reading speed, a direct performance assessment, through 6 months in eyes of patients with macular edema after retinal vein occlusion (RVO). DESIGN Two multicenter, double-masked, phase 3 trials in which participants with macular edema after branch RVO or central RVO were randomized 1:1:1 to monthly sham, ranibizumab, 0.3 mg, or ranibizumab, 0.5 mg, for 6 months. Community- and academic-based ophthalmology practices specializing in retinal diseases. Seven hundred eighty-nine eyes of 789 participants who were at least aged 18 years with macular edema secondary to retinal vein occlusion in the branch vein occlusion (BRAVO) and central vein occlusion (CRUISE) trials. Eyes were randomized 1:1:1 to 1 of 3 groups for monthly injections for 6 months: sham (132 in BRAVO and 130 in CRUISE), intravitreal ranibizumab, 0.3 mg (134 in BRAVO and 132 in CRUISE), and intravitreal ranibizumab, 0.5 mg (131 in BRAVO and 130 in CRUISE). Patients were able to receive macular laser after 3 months if they met prespecified criteria. Reading speed in the study eye was measured with enlarged text (letter size equivalent to approximately 20/1500 at the test distance) at baseline and 1, 3, and 6 months. The number of correctly read words per minute (wpm) was reported. The reading speed test requires a sixth-grade reading level and does not account for literacy or cognitive state. RESULTS In patients with branch RVO, the mean gain for the 0.5-mg group was 31.3 wpm compared with 15.0 wpm in sham-treated eyes (difference, 16.3 wpm; P = .007) at 6 months. In patients with central RVO, the mean gain for the 0.5-mg group was 20.5 wpm compared with 8.1 wpm in sham-treated eyes (difference, 12.4 wpm; P = .01) at 6 months. A gain of 15 or more letters of best-corrected visual acuity letter score corresponded to an increase in reading speed of 12.3 wpm and 15.8 wpm in patients with branch and central RVO, respectively. These results suggest that patients with macular edema after RVO treated monthly with ranibizumab are more likely to have improvements in reading speed of the affected eyes through 6 months compared with sham treatment. These results demonstrate the relevance of the treatment benefit to functional visual gain. clinicaltrials.gov Identifier: NCT00486018 and NCT00485836.

Dexamethasone implants in retinal vein occlusion: 12-month clinical effectiveness using repeat injections as-needed

ObjectiveTo report the 12-month outcomes of the dexamethasone intravitreal implant in retinal vein occlusion (RVO), using an as-needed repeat injection protocol.DesignRetrospective consecutive case series of 51 eyes of 49 patients...

Electroretinographic Effects of Omega-3 Fatty Acid Supplementation on Dry Age-Related Macular Degeneration

To evaluate the effects of high-dose oral omega-3 fatty acid supplementation on electroretinography and omega-3 index in patients with dry age-related macular degeneration. Single institution, prospective, nonrandomized, noncomparative interventional case series comprising 34 eyes of 17 patients older than 50 years of age with early to intermediate age-related macular degeneration. Patients received oral supplementation with 4 g of omega-3 fatty acids daily (840 mg eicosapentaenoic acid/2520 mg docosahexaenoic acid) for 6 months. The main outcome measures included Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, change in N1 and P1 peak amplitudes on multifocal electroretinographic testing, and change in serum omega-3 index. Mean baseline Early Treatment Diabetic Retinopathy Study best-corrected visual acuity letter score was 77 letters (Snellen equivalent of 20/32). There were no statistically significant changes in visual acuity (P = .12) or retinal function by multifocal electroretinographic testing. Serum omega-3 index increased by an average of 7.6% during the course of the study (P < .001). Study limitations included the relatively short duration of the study and small number of participants. Short-term supplementation with high doses of omega-3 fatty acids does not result in any measurable changes in visual acuity or retinal function by multifocal electroretinographic testing. Dietary supplementation with 4 g of omega-3 fatty acids results in a significant increase in serum omega-3 index in patients with dry age-related macular degeneration and may provide a useful clinical measure for future studies. clinicaltrials.gov Identifier: NCT01258335.

Predictive Value in Retinal Vein Occlusions of Early Versus Late or Incomplete Ranibizumab Response Defined by Optical Coherence Tomography

To determine if optical coherence tomography (OCT) at baseline or month 3 in the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Treatment of Macular Edema following Central Retinal Vein Occlusion: Evaluation of Efficacy and Safety (CRUISE) studies provides information that predicts visual outcome. Post hoc analysis from 2 prospective, randomized, controlled clinical trials. Three hundred ninety-seven patients from the BRAVO study and 392 patients from the CRUISE study. Time-domain OCT imaging data were analyzed. Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6 and month 12. Among ranibizumab-treated patients, 71.2% (0.3 mg) and 78.5% (0.5 mg) in the CRUISE study and 79.1% (0.3 mg) and 84.7% (0.5 mg) in the BRAVO study had central foveal thickness (CFT) of 250 μm or less at month 3 and therefore were categorized as early ranibizumab responders. Early ranibizumab responders had excellent visual outcomes regardless of ranibizumab dose; mean improvement in BCVA letter score at 6 and 12 months was 15.0 to 16.5 (central retinal vein occlusion [CRVO]) and 17.4 to 19.1 (branch retinal vein occlusion [BRVO]). Late or incomplete ranibizumab responders with CRVO (CFT >250 μm at month 3) did not fare as well as early responders if they were treated with 0.3 mg ranibizumab (month 6, P = 0.012). At month 6, compared with ranibizumab-treated CRVO patients with resolved cystoid macular edema (CME) at month 3, those with persistent CME did worse, on average, and significantly so for 0.5 mg (13.1 vs. 18.6; P = 0.027). At baseline, subretinal fluid (SRF) was present in 57% of patients with CRVO and in 45% of patients with BRVO; its presence did not portend a poor outcome in patients treated with ranibizumab for whom SRF was eliminated in almost all by month 3. At month 3 of ranibizumab treatment, OCT images provide predictive information for patients with CRVO, but not for those with BRVO. Visual outcome at months 6 and 12 was reduced in 0.5 mg ranibizumab-treated patients with CRVO who had persistent CME at month 3. It also was reduced in CRVO for those with CFT of more than 250 μm at month 3 who were treated with 0.3 mg ranibizumab. The findings suggest that late or incomplete responders may need careful follow-up. Proprietary or commercial disclosure may be found after the references.

Five-year results of photodynamic therapy with verteporfin for Japanese patients with neovascular age-related macular degeneration

PurposeTo describe the treatment outcome of photodynamic therapy (PDT) in Japanese patients with age-related macular degeneration (AMD) followed for 5 years.Patients and methodsWe retrospectively reviewed clinical charts of 51 patients with AMD. Thirty-one eyes of typical AMD (tAMD) and 20 eyes of polypoidal choroidal vasculopathy (PCV) were evaluated.ResultsThe mean logarithm of the minimum angle of resolution (logMAR) vision of all AMD patients was 0.807 at the baseline examination and 0.937 at the 5 year examination. Mean visual acuity letter score loss is similar between patients with tAMD (−7.25) and with PCV (−5.36) at the month 60 examination. The patients with lesions of classic choroidal neovascularization (CNV) had 10.0 letters loss, but the patients with lesions of occult CNV had only 1.43 letters loss. The number of retreatments peaked in year 1 and declined immediately for patients with tAMD, but patients with PCV had significantly more frequent retreatments in the years 3 and 4 than patients with tAMD (P = 1.48 × 10−2, 5.96 × 10−3, respectively).ConclusionVisual outcomes in patients with Japanese patients with AMD treated with PDT after 5-year follow up were worse than that in short-term follow up reported previously. In addition, the difference in visual prognosis between tAMD and PCV was not demonstrated after long-term follow-up.

Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment: Three-Year Randomized Trial Results

<h3>Objective</h3> To report the 3-year follow-up results within a previously reported randomized trial evaluating prompt versus deferred (for ≥24 weeks) focal/grid laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic macular edema (DME). <h3>Design</h3> Multicenter, randomized clinical trial. <h3>Participants</h3> Three hundred sixty-one participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. <h3>Methods</h3> Ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and random assignment to prompt or deferred (≥24 weeks) focal/grid laser treatment. <h3>Main Outcome Measures</h3> Best-corrected visual acuity and safety at the 156-week (3-year) visit. <h3>Results</h3> The estimated mean change in visual acuity letter score from baseline through the 3-year visit was 2.9 letters more (9.7 vs. 6.8 letters; mean difference, 2.9 letters; 95% confidence interval, 0.4–5.4 letters; <i>P</i> = 0.02) in the deferral group compared with the prompt laser treatment group. In the prompt laser treatment group and deferral group, respectively, the percentage of eyes with a ≥10-letter gain/loss was 42% and 56% (<i>P</i> = 0.02), whereas the respective percentage of eyes with a ≥10-letter gain/loss was 10% and 5% (<i>P</i> = 0.12). Up to the 3-year visit, the median numbers of injections were 12 and 15 in the prompt and deferral groups, respectively (<i>P</i> = 0.007), including 1 and 2 injections, respectively, from the 2-year up to the 3-year visit. At the 3-year visit, the percentages of eyes with central subfield thickness of 250 μm or more on time-domain optical coherence tomography were 36% in both groups (<i>P</i> = 0.90). In the deferral group, 54% did not receive laser treatment during the trial. Systemic adverse events seemed to be similar in the 2 groups. <h3>Conclusions</h3> These 3-year results suggest that focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better, and possibly worse, for vision outcomes than deferring laser treatment for 24 weeks or more in eyes with DME involving the fovea and with vision impairment. Some of the observed differences in visual acuity at 3 years may be related to fewer cumulative ranibizumab injections during follow-up in the prompt laser treatment group. Follow-up through 5 years continues. <h3>Financial Disclosure(s)</h3> Proprietary or commercial disclosure may be found after the references.

Association of outer retinal layer morphology with visual acuity in patients with retinal vein occlusion: SCORE Study Report 13

To assess associations between visual acuity (VA) and the status of the photoreceptor inner segment-outer segment (IS-OS) junction in a subset of patients in the Standard Care vs COrticosteroid for REtinal Vein Occlusion (SCORE) Study. High-resolution time domain optical coherence tomography (OCT) scans of study eyes from a single site participating in the SCORE Study were evaluated. Integrity of the IS-OS junction in the central subfield was evaluated using a three-step scale: absent, abnormal or normal. Associations of the IS-OS status with ETDRS VA letter score and center point thickness (CPT) were investigated. Baseline OCTs of 42 eyes were evaluated. The IS-OS junction was absent in 30 (71%) and abnormal in 12 (29%). At month 12, the IS-OS junction was absent in 18 (43%), abnormal in 12 (28%), and normal in 12 (28%) eyes. At baseline, IS-OS status was significantly associated with CPT, but not with VA. At month 12, IS-OS status was significantly associated with CPT and VA, that is, absent or abnormal IS-OS was associated with increased CPT and worse VA. Change in IS-OS status was not associated with change in CPT (P=0.8). Worsening of IS-OS status was associated with loss of VA and improvement in IS-OS status to normal was associated with gain in VA (P=0.03). In this data set with long-term follow-up of OCTs as part of the SCORE Study, there is a correlation between change in IS-OS status and VA. This supports further evaluation of outer retinal morphology in larger data sets.

Ranibizumab for Macular Edema Due to Retinal Vein Occlusions: Long-term Follow-up in the HORIZON Trial

To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO). Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials. We included 304 patients who completed BRAVO and 304 patients who completed CRUISE. Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria. Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness. In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), -2.3 (0.3/0.5 mg), and -0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was -4.2 (sham/0.5 mg), -5.2 (0.3/0.5 mg), and -4.1 (0.5 mg), respectively. No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months.

Prospective Study of a Fluocinolone Acetonide Implant for Chronic Macular Edema from Central Retinal Vein Occlusion: Thirty-Six-Month Results

To assess long-term visual outcomes and adverse events from a fluocinolone acetonide (FA) sustained drug delivery implant in eyes with chronic macular edema from central retinal vein occlusion (CRVO). Prospective interventional case series. A total of 24 eyes of 23 subjects with vision loss associated with chronic macular edema from CRVO. Implantation of an intravitreal FA sustained drug delivery system. The primary outcome measure was mean Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity letter score at 36 months after implantation. Secondary outcome measures included number of subjects with ≥ 10-letter improvement in ETDRS letter score, central foveal thickness (CFT), total macular volume, and intraocular pressure (IOP). At 1, 2, and 3 years after implantation, mean visual acuity showed gains of 4.5 (P = 0.52), 8.2 (P = 0.07), and 3.4 (P = 0.64) letters, respectively, and 32%, 56%, and 50% of study eyes, respectively, showed at least a 10-letter gain in ETDRS score. At these same time points, mean CFT improved by 247 (44%; P = 0.002), 212 (38%; P < 0.001), and 250 μm (45%; P<0.001), respectively. During the study period, all phakic eyes ultimately underwent cataract extraction, and 5 eyes underwent glaucoma surgery. The FA drug delivery system provided sustained visual acuity and anatomic benefit in patients with macular edema from CRVO, and it has promise as a therapeutic option for selected patients with this condition. The main complications were cataract and elevated IOP. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Sustained Benefits from Ranibizumab for Macular Edema following Central Retinal Vein Occlusion: Twelve-Month Outcomes of a Phase III Study

Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO). Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial. We included 392 patients with macular edema after CRVO. Eligible patients were randomized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. After 6 months, all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab. Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 12, additional parameters of visual function, central foveal thickness (CFT), and other anatomic changes were assessed. Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 13.9 (11.2-16.5) and 13.9 (11.5-16.4) in the 0.3 mg and 0.5 mg groups, respectively, and 7.3 (4.5-10.0) in the sham/0.5 mg group (P<0.001 for each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups, respectively, and 33.1% in the sham/0.5 mg group. On average, there was a marked reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group to the level of the ranibizumab groups, which was sustained through month 12. No new ocular or nonocular safety events were identified. On average, treatment with ranibizumab as needed during months 6 through 11 maintained the visual and anatomic benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after CRVO, with low rates of ocular and nonocular safety events. After sham injections for 6 months, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab treatment groups and an improvement in BCVA, but not to the same level as that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after CRVO. Proprietary or commercial disclosure may be found after the references.

RANDOMIZED TRIAL EVALUATING SHORT-TERM EFFECTS OF INTRAVITREAL RANIBIZUMAB OR TRIAMCINOLONE ACETONIDE ON MACULAR EDEMA AFTER FOCAL/GRID LASER FOR DIABETIC MACULAR EDEMA IN EYES ALSO RECEIVING PANRETINAL PHOTOCOAGULATION

To evaluate 14-week effects of intravitreal ranibizumab or triamcinolone in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation. Three hundred and forty-five eyes with a visual acuity of 20/320 or better, center-involved diabetic macular edema receiving focal/grid laser, and diabetic retinopathy receiving prompt panretinal photocoagulation were randomly assigned to sham (n = 123), 0.5-mg ranibizumab (n = 113) at baseline and 4 weeks, and 4-mg triamcinolone at baseline and sham at 4 weeks (n = 109). Treatment was at investigator discretion from 14 weeks to 56 weeks. Mean changes (±SD) in visual acuity letter score from baseline were significantly better in the ranibizumab (+1 ± 11; P < 0.001) and triamcinolone (+2 ± 11; P < 0.001) groups compared with those in the sham group (-4 ± 14) at the 14-week visit, mirroring retinal thickening results. These differences were not maintained when study participants were followed for 56 weeks for safety outcomes. One eye (0.9%; 95% confidence interval, 0.02%-4.7%) developed endophthalmitis after receiving ranibizumab. Cerebrovascular/cardiovascular events occurred in 4%, 7%, and 3% of the sham, ranibizumab, and triamcinolone groups, respectively. The addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study.

CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration

AimsTo investigate an association between genotype for three single nucleotide polymorphisms strongly associated with the development of age-related macular degeneration (AMD) and the early response to treatment with intravitreal ranibizumab...

Expanded 2-Year Follow-up of Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

To report expanded 2-year follow-up of a previously reported randomized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Multicenter, randomized clinical trial. A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. Continuation of procedures previously reported for the randomized trial. Best-corrected visual acuity and safety at the 2-year visit. At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness ≥250 μm were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.

Ranibizumab: in macular oedema following retinal vein occlusion.

Ranibizumab (Lucentis®), a recombinant humanized IgG(1) κ isotype monoclonal antibody fragment, is approved in the US for the treatment of macular oedema following retinal vein occlusion (RVO). It binds to the receptor-binding site of active forms of vascular endothelial growth factor-A, inhibiting its biological activity. In two large, well designed, phase III trials in patients with macular oedema following branch RVO (BRVO) or central RVO (CRVO), monthly intravitreal injections of ranibizumab 0.5 mg were associated with significantly greater improvement from baseline in mean best-corrected visual acuity letter score (measured on the Early Treatment Diabetic Retinopathy Study chart) in the study eye at 6 months (primary endpoint) than sham injections. Moreover, ranibizumab was significantly more effective than sham injections with regard to improvements in central foveal thickness at 6 months, as well as several other visual acuity measures. Ranibizumab was generally well tolerated in patients with macular oedema following CRVO or BRVO. Overall, the most common adverse events with ranibizumab were consistent with the adverse event profile previously reported in patients with age-related macular degeneration.

Retinal Nerve Fiber Layer Thickness in Children With Optic Pathway Gliomas

To determine the relationship of high-contrast visual acuity (VA) and low-contrast letter acuity with retinal nerve fiber layer (RNFL) thickness in children with optic pathway gliomas. Cross-sectional convenience sample, with prospective data collection, from a tertiary care children's hospital of patients with optic pathway gliomas associated with neurofibromatosis type 1, sporadic optic pathway gliomas, and neurofibromatosis type 1 without optic pathway gliomas. Patients underwent best-corrected VA testing using surrounded H, O, T, V optotypes and low-contrast letter acuity (5%, 2.5%, and 1.25% low-contrast Sloan letter charts). Mean RNFL thickness (micrometers) was measured by a Stratus optical coherence tomography device (Carl Zeiss Meditec) using the fast RNFL thickness protocol. Eyes were classified as having abnormal vision if they had high-contrast VA of more than 0.1 logarithm of the minimal angle of resolution units or visual field loss. The association of subject age, glioma location, and RNFL thickness with both VA and low-contrast letter acuity scores was evaluated by 1-way analysis of variance and linear regression, using the generalized estimating equation approach to account for within-patient intereye correlations. Eighty-nine eyes of patients with optic pathway gliomas were included, and 41 were classified as having abnormal VA or visual field loss. Reduced RNFL thickness was associated significantly with higher logarithm of the minimal angle of resolution scores for both VA (P < .001) and all low-contrast letter acuity charts (P < .001) when accounting for age and glioma location. Eyes of most children with optic pathway gliomas and decreased RNFL thickness had abnormal VA or visual field loss.

Visual Acuity Testing Using Autorefraction or Pinhole Occluder Compared with a Manual Protocol Refraction in Individuals with Diabetes

To compare visual acuity (VA) scores obtained after autorefraction or using a pinhole occluder to scores obtained after refraction according to a standard clinical research protocol. Prospective, comparative case series. One hundred ten study participants (209 eyes) with diabetes mellitus and a broad range of diabetic retinopathy severity and VA. We measured VA after autorefraction by a Topcon KR-8000 autorefractor as well as after a Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction. The order of testing was randomized and examiners were masked to the source of each refraction. A second VA measurement, utilizing an identical DRCR.net manual refraction, was made in a subset of eyes (n = 144; 69%) to establish test-retest variability for comparison purposes. All eyes underwent VA testing using a pinhole occluder. Best corrected VA as measured by the Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Test (E-ETDRS). In all eyes, the median E-ETDRS VA letter score (EVA) obtained after manual refraction (MR-EVA) was 69 (Snellen equivalent 20/40), ranging from 4 to 93 (20/800 to 20/16). The median MR-EVA was slightly better than the median EVA obtained after autorefraction (AR-EVA), with a median difference (AR-EVA - MR-EVA) of -1 letter (25th, 75th percentiles, -4, 2 letters). The absolute difference between AR-EVA and MR-EVA was similar to the test-retest variability of MR-EVA alone. In contrast, MR-EVA was better than EVA obtained using a pinhole occluder (PH-EVA; median PH-EVA - MR-EVA, -4 letters [-9, 0]), and had significantly less test-retest variability (P<0.001). Generally, the spherical equivalent of autorefraction was slightly more hyperopic (or less myopic) than the spherical equivalent of manual refraction (median difference, +0.25 diopters [0, +0.63]). Given the substantial time and effort required for training and certification of study protocol refractionists, and the similarity between AR-EVA and MR-EVA, further evaluation of autorefraction, but not pinhole occluder testing, as an alternative to the current clinical research gold standard of ETDRS protocol manual refraction in study participants with diabetic retinopathy is warranted.